Performance of serological tests available in Brazil for the diagnosis of human visceral leishmaniasis

Abstract

Background Visceral leishmaniasis (VL) is the most severe form of leishmaniasis and is potentially fatal if not diagnosed and treated. Accurate and timely diagnosis is considered one of the pillars needed for the reduction in disease-related lethality. Brazil is currently one of the three eco-epidemiological hotspots for this disease. Several serological tests are commercially available in this country for VL diagnosis, although information on the performance of these tests is fragmented and insufficient. The aim of this study was to directly compare the performance of six commercial kits: three enzyme-linked immunosorbent assays (ELISAs), two immunofluorescence antibody tests (IFATs), one immunochromatographic test (ICT), besides one ICT, currently not commercially available in Brazil and one in-house direct agglutination test (DAT-LPC), not yet marketed. Methodology/Principal findings A panel of 236 stored samples from patients with clinically suspected VL, including 77 HIV-infected patients, was tested. IT-LEISH and DAT-LPC showed the highest accuracy rate among the non-HIV-infected patients, 96.2% [CI95%: 92.8–99.7%] and 95.6% [CI95%: 91.9–99.3%], respectively. For the ELISA tests evaluated, the maximum accuracy was 91.2%, and in the inter HIV-status group analysis, no significant differences were observed. For both IFATs evaluated, the maximum accuracy was 84.3%, and a lower accuracy rate was observed among the HIV-infected patients (p = 0.039) than among the non-HIV-infected patients. The DAT-LPC was the most accurate test in the HIV-infected patients (p≤0.115). In general, no significant difference in accuracy was observed among the VL-suspected patients stratified by age. Conclusions/Significance In summary, the differences in the performance of the tests available for VL in Brazil confirm the need for local studies before defining the diagnostic strategy.

Performance of rK39-based immunochromatographic rapid diagnostic test for serodiagnosis of visceral leishmaniasis using whole blood, serum and oral fluid

“…ELISA demonstrated a poor specificity, ranging from 38.5-71.4% (56.0% in the total of samples), resulting in a low LR+ (2.15; 95%CI: 1.70-2.72) and a low accuracy (78.1%; 95%CI: 72.0-83.5). Other authors also obtained low specificity using total antigen-based ELISA [40][41][42]. IFA showed low accuracy (84.6%; 95%CI: 79.1-89.2) mostly due to the low sensitivity, ranging from 60.0-85.2% (80.6% in the total of samples), corroborating results obtained by other authors [31,40,41,43] The variable sensitivity of RDT depending on the locality may be attributable to the parasite diversity.…”

“…Other authors also obtained low specificity using total antigen-based ELISA [40][41][42]. IFA showed low accuracy (84.6%; 95%CI: 79.1-89.2) mostly due to the low sensitivity, ranging from 60.0-85.2% (80.6% in the total of samples), corroborating results obtained by other authors [31,40,41,43] The variable sensitivity of RDT depending on the locality may be attributable to the parasite diversity. A study using multi-locus microsatellite typing revealed the presence of 67 genotypes of L. infantum in 162 strains from 17 Brazilian states and 11 from one locality in Paraguay.…”

“…Concerning ELISA and IFA, we obtained unsatisfactory performance for the diagnosis of VL compared to Kalazar Detect and IT-Leish, as found by other studies [41]. ELISA demonstrated a poor specificity, ranging from 38.5-71.4% (56.0% in the total of samples), resulting in a low LR+ (2.15; 95%CI: 1.70-2.72) and a low accuracy (78.1%; 95%CI: 72.0-83.5).…”

Evaluation of six commercial kits for the serological diagnosis of Mediterranean visceral leishmaniasis

“…In this context, commercial kits may offer more uniform procedures for antigen preparation, compared with home-made assays, and provide standardized experimental conditions. However, large-scale studies comparing the performances of commercial assays are lacking [5,7]. A recent study in Brazil compared, for the first time, different kits tested in the same condition and in the same population [5].…”

“…The search of specific antibodies in serum or plasma, while requiring non-invasive sampling, remains the most widely used method for VL diagnosis. However, serological tests tend to be less sensitive in children younger than three years [4,5] and in immunocompromised patients [6,7]. Currently, molecular detection is considered the most reliable method [8,9], with a sensitivity higher than 95% for PCR analysis on peripheral blood [10].…”