Validação diagnóstica do imunoensaio enzimático e do ensaio de fluxo lateral na detecção antigênica de histoplasma capsulatum em pessoas vivendo com HIV/AIDS: estudo em centro de referência no Brasil

Abstract

Disseminated histoplasmosis (DH) is a systemic fungal infection associated with high morbidity and mortality among people living with HIV/AIDS (PLWHA), particularly in cases of advanced immunosuppression. Its nonspecific presentation and overlap with other opportunistic infections make early diagnosis challenging. Conventional methods, such as culture and histopathology, have low sensitivity and prolonged turnaround time. In this context, urinary antigen detection tests have emerged as a rapid and noninvasive alternative. This study evaluated the diagnostic performance of IMMY ELISA and MVD LFA for the detection of Histoplasma capsulatum in PLWHA with suspected DH. This was a retrospective diagnostic accuracy study conducted at a referral center in Brazil between January and December 2025, involving hospitalized patients with suspected opportunistic infections. The reference standard was defined by proven or probable histoplasmosis cases, established based on clinical-laboratory, microbiological, histopathological, and/or serological criteria. A total of 300 samples were screened, of which 214 were included in the final analysis, with 29 classified as proven or probable histoplasmosis and 185 as without histoplasmosis. IMMY ELISA demonstrated excellent diagnostic performance, with sensitivity of 96.6%, specificity of 96.2%, and area under the curve (AUC) of 0.98. The positive predictive value (PPV) was 80.0% and the negative predictive value (NPV) was 99.4%. The optimal ELISA cutoff, determined by ROC curve analysis based on the Youden index, was 1.055 ng/mL. MVD LFA showed sensitivity of 96.6% and specificity of 87.6%, with PPV of 54.9% and NPV of 99.4%, demonstrating good overall accuracy but lower specificity compared with ELISA. Antigenuria was detected in 13.08% of the cohort, resulting in a 16.9% increase in case detection compared with culture alone. Ninety-day mortality among patients with histoplasmosis was 30%, and an exploratory survival analysis suggested a trend toward worse prognosis associated with higher urinary antigen concentrations. In conclusion, both tests demonstrated high diagnostic performance for histoplasmosis detection in PLWHA, particularly regarding high sensitivity, elevated negative predictive value, and potential clinical impact on early case identification in endemic settings, reinforcing their applicability as complementary tools to traditional diagnostic methods.