NEW YORK — Serological tests for visceral leishmaniasis (VL) currently available in Brazil — a hotspot for the tropical disease — vary significantly in their performance, highlighting the need for more stringent validation before such diagnostics are released to the market, according to a new study.
VL is the most severe form of the parasitic infection leishmaniasis and is typically fatal if left untreated. Demonstration of Leishmania parasites in bone marrow aspirates or other biological specimens is the gold standard for disease diagnosis but can be a time-consuming process, requiring health professionals to collect samples and perform parasitological exams.
A number of serological tests are available for VL diagnosis in Brazil, where 97 percent of reported VL cases in South America occur, but there has been no effort to comparatively analyze the performance of these assays, particularly in the context of HIV co-infection.
To address this issue, a team led by scientists from the Oswaldo Cruz Foundation set out to evaluate the performance of six VL diagnostic kits commercially available in Brazil — three enzyme-linked immunosorbent assays (ELISAs), two immunofluorescence antibody tests (IFATs), and one immunochromatographic test (ICT) — as well as an ICT and an in-house direct agglutination test (DAT-LPC) that are not currently on the market.
In their study, which appears in PLOS Neglected Tropical Diseases, the investigators tested a panel of 236 stored samples from patients with clinically suspected VL, including 77 HIV-infected patients. One of the ICTs, made by Bio-Rad Laboratories, had the highest accuracy rate among non-HIV-infected patients at 96.2 percent, followed by the DAT-LPC at 95.6 percent. The maximum accuracy in non-HIV-infected patients for the ELISA tests was 91.2 percent, and 87.4 percent for the IFATs.
The performance of all the tests was impacted by HIV infection, with the DAT-LPC having the highest accuracy at 89.6 percent among individuals with HIV. The accuracy of Bio-Rad's test, meanwhile, fell to 80.5 percent in this patient group. No significant difference in accuracy was observed among VL-suspected patients stratified by age.
Currently, there is no consensus about the minimum performance required for a VL diagnostic test, the study's authors noted. However, in 2007, a team that included scientists from the Institute of Tropical Medicine Antwerp and the World Health Organization recommended that such tests should have a sensitivity and specificity of at least 95 percent and 98 percent, respectively. Based on these guidelines, "none of the diagnostic tests evaluated here are satisfactory," the researchers wrote in PLOS Neglected Tropical Diseases. "In this sense, questions emerge from these results surrounding the adequacy (or inadequacy) of the current tests as efficient tools" for tracking VL.
Taken together, the study's results reveal significant differences in the performance of different serological tests for VL and confirm that the use of serology should be qualified with previous information on the performance of the tests, the researchers wrote.
The findings also highlight the need for "more stringent criteria for the registration of diagnostic products in Brazil, including the requirement to carry out validation studies before marketing" they added. "In a future, broader analysis, in addition to performance, other aspects of these tests should be considered before a diagnostic strategy is defined, such as cost-effectiveness, national production/autonomy, and accessibility."