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 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 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 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 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.
Background A Diagnostic Laboratory Hub (DLH) was set up in Guatemala to provide opportunistic infection (OI) diagnosis for people with HIV (PWH). Methods Patients newly presenting for HIV, PWH not receiving antiretrovirals (ARVs) for >90 days but returned to care (Return/Restart), and PWH on ARVs with symptoms of OIs (ARV treatment) were prospectively included. Screening for tuberculosis, nontuberculous mycobacteria (NTM), histoplasmosis, and cryptococcosis was done. Samples were couriered to the DLH, and results were transmitted electronically. Demographic, diagnostic results, disease burden, treatment, and follow-up to 180 days were analyzed. Results In 2017, 1953 patients were included, 923 new HIV infections (an estimated 44% of all new HIV infections in Guatemala), 701 on ARV treatment, and 315 Return/Restart. Three hundred seventeen (16.2%) had an OI: 35.9% tuberculosis, 31.2% histoplasmosis, 18.6% cryptococcosis, 4.4% NTM, and 9.8% coinfections. Histoplasmosis was the most frequent AIDS-defining illness; 51.2% of new patients had <200 CD4 cells/mm3 with a 29.4% OI incidence; 14.3% of OIs in new HIV infections occurred with CD4 counts of 200–350 cells/mm3. OIs were the main risk factor for premature death for new HIV infections. At 180 days, patients with OIs and advanced HIV had 73-fold greater risk of death than those without advanced disease who were OI-free. Conclusions The DLH OI screening approach provides adequate diagnostic services and obtains relevant data. We propose a CD4 screening threshold of <350 cells/mm3. Mortality remains high, and improved interventions are required, including expansion of the DLH and access to antifungal drugs, especially liposomal amphotericin B and flucytosine.
Opportunistic infections (OIs) and advanced HIV disease (AHD) contribute to HIV-related mortality. Here, we analyzed the situation of AHD and OIs in a cohort of newly diagnosed HIV patients from Guatemala. We included 2127 adult patients from 13 facilities across the country during 2017 to 2018. Patients were screened for tuberculosis (TB), nontuberculous mycobacteria (NTM), histoplasmosis, and cryptococcal disease, independently of their CD4 cell count. Of the 2127 enrolled patients, 1682 (79.1%) had a CD4 cell count available; of which 52% presented with AHD. Of the Mayan population, 65% had AHD. The overall OI incidence was 21%. Histoplasmosis was the most frequent OI (7.9%), followed by TB (7.1%); 94.4% of these infections occurred in patients with a CD4 < 350 cells/mm3. Mortality at 180 days was significantly higher in those with OIs than without OIs (29.7% vs. 5.9%, p < 0.0001). In one year, this program decreased the OI mortality by 7% and increased the OI treatment by 5.1%. Early OI diagnosis and appropriate therapy reduced OI mortality among newly diagnosed HIV patients in Guatemala. Screening for OIs should be considered in all newly diagnosed HIV patients who have a CD4 cell count < 350 cells/mm3 or those without a CD4 cell count available. To improve results, interventions such as early HIV detection and access to flucytosine and liposomal amphotericin B are required.
Objectives: We evaluated the comparative performance of different assays used in a Diagnostic Laboratory Hub that linked 13 HIV healthcare facilities for the diagnosis of tuberculosis (TB), histoplasmosis, and cryptococcosis, and describing its functions in Guatemala compared with other National Reference Laboratories. Methods: The following diagnostic techniques were analyzed in 24 months (2017–2018) in a cohort of patients with HIV: smear microscopy, mycobacterial and fungal cultures, isolator blood culture, PCR assays, and antigen detection tests. Results: A total of 4245 patients were included, 716 (16.2%) had an opportunistic infection: 249 (34.7%) TB, 40 (5.6%) nontuberculous mycobacteria, 227 (31.7%) histoplasmosis, 138 (19.3%) cryptococcosis, and 62 (8.6%) had multiple opportunistic infections. Two hundred sixty-three [92.6%; 95% confidence interval (CI), 89–95.1] of TB cases were diagnosed by PCR. Urine antigen assay detected 94% (95% CI, 89–96) of the disseminated histoplasmosis cases. A lateral flow assay to detect cryptococcal antigen diagnosed 97% (95% CI, 93.3–98.7%) of the cryptococcal cases. In 85 patients (51.5%) with a cerobrospinal fluid sample, cryptococcal meningitis was diagnosed in 55 (64.7%), of which 18 (32.7%) were only detected by cryptococcal antigen. Conclusion: Validated commercial antigen tests, as used in this program, should be the new gold standard for histoplasmosis and cryptococcosis diagnosis. In their absence, 35% of disseminated histoplasmosis and 32.7% of cryptococcal meningitis cases would have been missed. Patients with multiple opportunistic infections were frequently diagnosed and strategies should be designed to screen patients irrespective of their clinical presentation. In low resource settings, Diagnostic Laboratory Hubs can deliver quality diagnostics services in record time at affordable prices.
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