Diagnostic accuracy of antigen detection in urine and molecular assays testing in different clinical samples for the diagnosis of progressive disseminated histoplasmosis in patients living with HIV/AIDS: A prospective multicenter study in Mexico

Abstract

Background The progressive disseminated histoplasmosis (PDH) has been associated with severe disease and high risk of death among people living with HIV (PLWHIV). Therefore, the purpose of this multicenter, prospective, double-blinded study done in ten Mexican hospitals was to determine the diagnostic accuracy of detecting Histoplasma capsulatum antigen in urine using the IMMY ALPHA Histoplasma EIA kit (IAHE), clarus Histoplasma GM Enzyme Immunoassay (cHGEI IMMY) and MiraVista Histoplasma Urine Antigen LFA (MVHUALFA); as well as the Hcp100 and 1281-1283220SCAR nested PCRs in blood, bone-marrow, tissue biopsies and urine. Methodology/Principal findings We included 415 PLWHIV older than 18 years of age with suspicion of PDH. Using as diagnostic standard recovery of H. capsulatum in blood, bone marrow or tissue cultures, or histopathological exam compatible, detected 108 patients (26%, [95%CI, 21.78–30.22]) with proven-PDH. We analyzed 391 urine samples by the IAHE, cHGEI IMMY and MVHUALFA; the sensitivity/specificity values obtained were 67.3% (95% CI, 57.4–76.2) / 96.2% (95% CI, 93.2–98.0) for IAHE, 91.3% (95% CI, 84.2–96.0) / 90.9% (95% CI, 87.0–94.0) for cHGEI IMMY and 90.4% (95% CI, 83.0–95.3) / 92.3% (95% CI, 88.6–95.1) for MVHUALFA. The Hcp100 nested PCR was performed on 393, 343, 75 and 297, blood, bone marrow, tissue and urine samples respectively; the sensitivity/specificity values obtained were 62.9% (95%CI, 53.3–72.5)/ 89.5% (95%CI, 86.0–93.0), 65.9% (95%CI, 56.0–75.8)/ 89.0% (95%CI, 85.2–92.9), 62.1% (95%CI, 44.4–79.7)/ 82.6% (95%CI, 71.7–93.6) and 34.9% (95%CI, 24.8–46.2)/ 67.3% (95%CI, 60.6–73.5) respectively; and 1281-1283220SCAR nested PCR was performed on 392, 344, 75 and 291, respectively; the sensitivity/specificity values obtained were 65.3% (95% CI, 55.9–74.7)/ 58.8% (95%CI, 53.2–64.5), 70.8% (95%CI, 61.3–80.2)/ 52.9% (95%CI, 46.8–59.1), 71.4% (95%CI, 54.7–88.2)/ 40.4% (95%CI, 26.4–54.5) and 18.1% (95%CI, 10.5–28.1)/ 90.4% (95%CI, 85.5–94.0), respectively. Conclusions/Significance The cHGEI IMMY and MVHUALFA tests showed excellent performance for the diagnosis of PDH in PLWHIV. The integration of these tests in clinical laboratories will certainly impact on early diagnosis and treatment.

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

“…The sensitivity, specificity, and accuracy of the assay were 90.4%, 92.3%, and 91.8%, respectively, for proven disseminated histoplasmosis. A high level of agreement (κ = 0.85) was also noted between this LFA and another EIA-based test [ 13 ]. Despite the different geographic location and patient population, these results are very much like ours.…”

Validation and Concordance Analysis of a New Lateral Flow Assay for Detection of Histoplasma Antigen in Urine

“…Overall, the MVD LFA and MVD EIA have good agreement, but the MVD LFA was more accurate than the MVD EIA; 96% (CI 90–99%) vs 82% (CI 73–89%). In a recent prospective study from Mexico involving 104 urine samples from patients with histoplasmosis and 287 from patients without, the sensitivity of the MVD LFA was 90% (CI 83–95%), specificity was 92% (CI 89–95), and accuracy was 92% (89–94) [ 17 ]. In the current study, the MVD LFA displayed a sensitivity, specificity, and accuracy of 96% for each.…”

“…In 2015, IMMY (Norman, OK, USA) developed the Clarus Histoplasma GM EIA, which is commercially available for individual lab use. Reports on the use of this assay have also described high sensitivity and specificity for the diagnosis of histoplasmosis in PLHIV [ 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ].…”

“…The MVD LFA is designed to be rapid, simple to perform, and portable, potentially making testing available to resource-challenged countries, where it is needed most. This LFA was recently validated in a multicenter cohort of PLHIV from Mexico, where it showed high performance, 92% accuracy, to diagnose histoplasmosis [ 17 ]. The aim of the current study was to evaluate the analytical performance of the MVD LFA assay and compare it to the MiraVista ® Histoplasma Ag quantitative enzyme immunoassays (MVD EIA), using a standard reference collection of urine samples from Colombian PLHIV.…”

Evaluation of OIDx Histoplasma Urinary Antigen EIA

“…In 2020, the rst WHO guidelines for the diagnosis and management of disseminated histoplasmosis among people living with HIV recommended Ag testing to diagnose histoplasmosis (1,2). Within the last decade, commercial assays for the detection of Histoplasma Ag have become available, providing the potential for transfer of this technology to resource-limited countries where histoplasmosis is endemic and the capacity to diagnose histoplasmosis is limited (3)(4)(5)(6)(7)(8)(9)(10).…”