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Guidelines for Diagnosing and Managing Disseminated Histoplasmosis among People Living with HIV [Internet]. Washington (DC): Pan American Health Organization; 2020 Apr.

Cover of Guidelines for Diagnosing and Managing Disseminated Histoplasmosis among People Living with HIV

Guidelines for Diagnosing and Managing Disseminated Histoplasmosis among People Living with HIV [Internet].

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ANNEX 3SYSTEMATIC REVIEW PICO 1: PERFORMANCE OF DIAGNOSTIC ASSAYS

Objectives

To evaluate the analytical performance of laboratory assays for diagnosing progressive disseminated histoplasmosis among people living with HIV.

Methods

Search methods

Databases: Medline (Ovid), Embase (Ovid), CAB Abstracts (Ovid), Global Health (Ovid), Scopus, the Cochrane Library, PubMed Central, and LILACS.

Run date: February 20, 2019 for the terms histoplasmosis, HIV, and terms for the diagnostics assays evaluated, including their synonyms, in the title, abstract, keywords, or subject headings. A broader search was also conducted in the same databases for histoplasmosis and HIV, and a diagnostic methods search filter was adapted from the McMaster Health Information Research Unit’s recommended search hedges. Searches were limited to the studies published in English, Spanish, and Portuguese.

Types of studies: systematic review

Studies related to validating Histoplasma laboratory assays. Studies were excluded if they did not focus on human application or were primarily case reports, clinical studies, environmental or epidemiological studies, or literature reviews with no validation component.

For studies related to validating laboratory assays for diagnosing histoplasmosis, we excluded studies of people without HIV, concordance studies, and studies without a clear number of people tested. To maintain the accuracy of the study, references were not included in the analysis if culture or histopathological analyses were not included to determine proven cases.

Statistical analysis and data synthesis: meta-analysis

Data from selected studies were extracted to reconstructed 2 by 2 tables. Meta-analysis was performed using STATA’s metandi and metan commands. Data were summarized using meta-analysis forest plot and hierarchical summary receiver operating characteristic (HSROC) curves.

Main results

Histoplasma antigen assays were determined to be the most accurate method for diagnosing progressive disseminated histoplasmosis in advanced HIV. Molecular assays appear promising for accurately diagnosing histoplasmosis, but consensus on the exact techniques is needed. Cultures showed variable sensitivity related to sample type and laboratory handling. Antibody assays presented high specificity but low sensitivity (19).

Authors’ conclusions

The results of the meta-analysis showed that laboratory assays based on detecting circulating Histoplasma antigen demonstrated the best analytical performance. Since there is very-low-certainty evidence, we recommend further prospective research.

Analytical performance of assays

Figure 1. Meta-analysis of the sensitivity for the culture assay’s analytical performance.

Figure 1Meta-analysis of the sensitivity for the culture assay’s analytical performance

Source: Caceres et al. J. Fungi 2019, 5(3), 76 [PMC free article: PMC6787751] [PubMed: 31426618] (19).

Figure 2. Meta-analysis of the antibody detection assay’s analytical performance: (A) sensibity, (B) specificity, and (C) Hierarchical summary receiver operating characteristic (HSROC).

Figure 2Meta-analysis of the antibody detection assay’s analytical performance: (A) sensibity, (B) specificity, and (C) Hierarchical summary receiver operating characteristic (HSROC)

Source: Caceres et al. J. Fungi 2019, 5(3), 76 [PMC free article: PMC6787751] [PubMed: 31426618] (19).

Figure 3. Meta-analysis of the antigen detection assay’s analytical performance: (A) sensibity, (B) specificity, and (C) Hierarchical summary receiver operating characteristic (HSROC).

Figure 3Meta-analysis of the antigen detection assay’s analytical performance: (A) sensibity, (B) specificity, and (C) Hierarchical summary receiver operating characteristic (HSROC)

Source: Caceres et al. J. Fungi 2019, 5(3), 76 [PMC free article: PMC6787751] [PubMed: 31426618] (19).

Figure 4. Meta-analysis of DNA detection (molecular) tests analytical performance: (A) sensitivity, (B) specificity, and (C) Hierarchical summary receiver operating characteristic (HSROC).

Figure 4Meta-analysis of DNA detection (molecular) tests analytical performance: (A) sensitivity, (B) specificity, and (C) Hierarchical summary receiver operating characteristic (HSROC)

Source: Caceres et al. J. Fungi 2019, 5(3), 76 [PMC free article: PMC6787751] [PubMed: 31426618] (19).

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Bookshelf ID: NBK587198

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