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

Abstract

Histoplasmosis is a major cause of mortality in people living with HIV (PLHIV). Rapid methods to diagnose Histoplasma capsulatum disease could dramatically decrease the time to initiate treatment, resulting in reduced mortality. The aim of this study was to validate a MiraVista® Diagnostics (MVD) Histoplasma urine antigen lateral flow assay (MVD LFA) for the detection of H. capsulatum antigen (Ag) in urine and compare this LFA against the MVista® Histoplasma Ag quantitative enzyme immunoassays (MVD EIA). We assessed the MVD LFA using a standardized reference panel of urine specimens from Colombia. We tested 100 urine specimens, 26 from PLHIV diagnosed with histoplasmosis, 42 from PLHIV with other infectious diseases, and 32 from non-HIV infected persons without histoplasmosis. Sensitivity and specificity of the MVD LFA was 96%, compared with 96% sensitivity and 77% specificity of the MVD EIA. Concordance analysis between MVD LFA and the MVD EIA displayed an 84% agreement, and a Kappa of 0.656. The MVD LFA evaluated in this study has several advantages, including a turnaround time for results of approximately 40 min, no need for complex laboratory infrastructure or highly trained laboratory personnel, use of urine specimens, and ease of performing.

Immunologic Diagnosis of Endemic Mycoses

“…Afterwards, a validation study was carried out on the MVista ® Diagnostics Histoplasma urine antigen lateral flow assay for antigen detection, and was associated with the MVista ® Histoplasma Ag quantitative ELISA. The sensitivity of both tests was 96%; however, the specificity was 96% and 77% for LFA and ELISA, respectively [ 89 ].…”

Updates on Histoplasmosis in Solid Organ Transplantation

“…This assay has the advantage of using urine specimens at the point of care and providing results within 40 min of specimen collection without the need for specialized equipment. Direct cross comparison of results from urine specimens between the LFA and EIA assay has demonstrated high concordance between the two assays, with high test sensitivity in immunosuppressed individuals with a higher burden of infection [ 44 •, 45 ]. However, both assays are limited by positive results due to cross-reactions with other fungal pathogens.…”

Methods of laboratory diagnosis of histoplasmosis – problems and prospects

“…Результаты исследования биологического материала от больных паракокцидиоидомикозом и криптококкозом оказались ложноположительными. Соответствие показателей теста бокового потока и иммуноферментного анализа было на уровне 84%, при этом время получения диагностического ответа сократилось до 40 минут, что делает данный тест наиболее перспективным [6].…”

“…После инвазии в ткани возбудитель гистоплазмоза включает механизмы, позволяющие ему эффективно преодолевать защитные барьеры макроорганизма и уклоняться от его иммунологического надзора. Ключевым этапом патогенеза считается конверсия мицелиальных структур в дрожжеподобные клетки, в ходе которой H. capsulatum поражает систему мононуклеарных макрофагов, препятствуя завершению фагоцитоза и формируя внутриклеточные ниши для вторичного распространения по другим органам и тканям [6]. Конверсия возбудителя гистоплазмоза является ключевой особенностью патогенеза, важным диагностическим критерием и неоспоримым доказательством причастности микромицета ко II группе патогенности.…”