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      Evaluation of a Histoplasma antigen lateral flow assay for the rapid diagnosis of progressive disseminated histoplasmosis in Colombian patients with AIDS

      1 , 2 , 3 , 4 , 1 , 1
      Mycoses
      Wiley

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          Abstract

          <p class="first" id="d14800119e109">Progressive disseminated histoplasmosis (PDH) is an important cause of mortality in persons living with HIV (PLHIV), especially in countries where patients have limited access to antiretroviral therapies and diagnostic testing. </p>

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          Diagnosis of histoplasmosis in immunosuppressed patients.

          To define the most appropriate studies for making a diagnosis of histoplasmosis in immunosuppressed patients. As is true of all fungal infections in immunosuppressed patients, heightened awareness of the epidemiology and clinical manifestations of histoplasmosis is essential in making an early diagnosis. Increasingly, Histoplasma antigen detection is used to help establish a diagnosis of histoplasmosis. Most of the reported data are on patients with AIDS, but limited data suggest the usefulness of this assay in other immunosuppressed patients as well. False positive reactions occur with other fungal infections, especially blastomycosis, and patients who have histoplasmosis may have a false positive serum Aspergillus galactomannan assay. The identification of the yeast phase of Histoplasma capsulatum in tissue biopsy samples and, uncommonly, in circulating blood phagocytes is also helpful in establishing a diagnosis quickly. PCR techniques have yet to prove useful for the rapid diagnosis of histoplasmosis, and serology is often negative in immunosuppressed patients. Culture remains definitive and should always be performed to confirm the results of the rapid diagnostic studies. Rapid techniques, mostly antigen detection in serum and urine and histopathological identification of Histoplasma capsulatum in tissues, are the most important rapid diagnostic tests for histoplasmosis in immunosuppressed patients.
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            Tuberculosis and histoplasmosis among human immunodeficiency virus-infected patients: a comparative study.

            In disease-endemic areas, histoplasmosis is the main differential diagnosis for tuberculosis among human immunodeficiency virus (HIV)-infected patients. However, no study has compared the two diseases. Thus, the objective of this study was to compare tuberculosis and histoplasmosis in HIV-infected patients. A population of 205 HIV-infected patients (99 with tuberculosis and 106 with histoplasmosis) hospitalized in Cayenne, French Guiana during January 1, 1997-December 31, 2008 were selected retrospectively from the French Hospital Database on HIV. Multivariate analysis showed that tuberculosis was associated with cough (adjusted odds ratio [AOR] = 0.20, 95% confidence interval [CI] = 0.05-0.73) and a C-reactive protein level > 70 mg/L (AOR = 0.98, 95% CI = 0.97-0.99). Variables associated with disseminated histoplasmosis were a γ-glutamyl transferase level > 72 IU/L (AOR = 4.99, 95% CI = 1.31-18.99), origin from French Guiana (AOR = 5.20, 95% CI = 1.30-20.73), disseminated localization (AOR = 6.40, 95% CI = 1.44-28.45), a concomitant opportunistic infection (AOR = 6.71, 95% CI = 1.50-29.96), a neutrophil count < 2,750 cells/mm(3) (AOR = 10.54, 95% CI = 2.83-39.24), a CD4 cell count < 60 cells/mm(3) (AOR = 11.62, 95% CI = 2.30-58.63), and a platelet count < 150,000/mm(3) (AOR = 19.20, 95% CI = 3.35-110.14). Tuberculosis and histoplasmosis have similarities, but some factors show a greater association with one of these diseases. Thus, adapted therapeutic choices can be made by using simple clinical and paraclinical criteria.
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              Multicenter Validation of Commercial Antigenuria Reagents To Diagnose Progressive Disseminated Histoplasmosis in People Living with HIV/AIDS in Two Latin American Countries

              Histoplasmosis is an important cause of mortality in patients with AIDS, especially in countries with limited access to antiretroviral therapies and diagnostic tests. However, many disseminated infections in Latin America go undiagnosed. A simple, rapid method to detect Histoplasma capsulatum infection in regions where histoplasmosis is endemic would dramatically decrease the time to diagnosis and treatment, reducing morbidity and mortality. The aim of this study was to validate a commercial monoclonal Histoplasma galactomannan (HGM) enzyme-linked immunosorbent assay (Immuno-Mycologics [IMMY], Norman, OK, USA) in two cohorts of people living with HIV/AIDS (PLHIV). We analyzed urine samples from 589 people (466 from Guatemala and 123 from Colombia), including 546 from PLHIV and 43 from non-PLHIV controls. Sixty-three of these people (35 from Guatemala and 28 from Colombia) had confirmed histoplasmosis by isolation of H. capsulatum . Using the standard curve provided by the quantitative commercial test, the sensitivity was 98% (95% confidence interval [CI], 95 to 100%) and the specificity was 97% (95% CI, 96 to 99%) (cutoff = 0.5 ng/ml). Semiquantitative results, using a calibrator of 12.5 ng/ml of Histoplasma galactomannan to calculate an enzyme immunoassay index value (EIV) for the samples, showed a sensitivity of 95% (95% CI, 89 to 100%) and a specificity of 98% (95% CI, 96 to 99%) (cutoff ≥ 2.6 EIV). This relatively simple-to-perform commercial antigenuria test showed a high performance with reproducible results in both countries, suggesting that it can be used to detect progressive disseminated histoplasmosis in PLHIV in a wide range of clinical laboratories in countries where histoplasmosis is endemic.
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                Author and article information

                Journal
                Mycoses
                Mycoses
                Wiley
                0933-7407
                1439-0507
                November 27 2019
                February 2020
                November 27 2019
                February 2020
                : 63
                : 2
                : 139-144
                Affiliations
                [1 ]Centers for Disease Control and Prevention (CDC) Atlanta GA USA
                [2 ]Studies in Translational Microbiology and Emerging Diseases (MICROS) Research Group School of Medicine and Health Sciences Universidad del Rosario Bogota Colombia
                [3 ]Hospital La Maria Medellin Colombia
                [4 ]Universidad CES Medellin Colombia
                Article
                10.1111/myc.13023
                31625627
                a755c511-84ee-4742-8d0a-4a56d6c78e0e
                © 2020

                http://onlinelibrary.wiley.com/termsAndConditions#vor

                http://doi.wiley.com/10.1002/tdm_license_1.1

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