Rapid test for Mycobacterium leprae infection: a practical tool for leprosy

Detection of infection with Mycobacterium leprae allows timely prophylactic treatment, thereby reducing transmission as well as the risk of permanent, leprosy-associated nerve damage. However, since there is no worldwide-implemented standard test for M. leprae infection, detection of infection in asymptomatic individuals remains a major challenge for control programs in endemic areas. In previous studies, we developed and field-tested a lateral flow assay (LFA) quantitatively detecting human IgM against M. leprae-specific phenolic glycolipid I (anti-PGL-I), a marker for both active and past infection. This rapid test utilizes luminescent, background-free, up-converting reporter particles (UCP) and immunochromatography (i.e. the UCP-LF test platform) for accurate quantitation of anti-PGL-I IgM without operator bias. The aim of this study was to evaluate the final version of this quantitative UCP-based rapid test (i.e. PGL-I QURapid), using serum and fingerstick blood (FSB).

The test comprises a lateral flow strip, in a standard plastic or biodegradable cassette. It can be provided with a humanized, recombinant control to monitor test performance and calculate accurate anti-PGL-I IgM levels. The performance of this QUR-test was assessed using serum and FSB from patients with leprosy (n = 214), tuberculosis (n = 20), buruli ulcer (n = 19), leishmaniasis (n = 14), non-tuberculous mycobacterial (n = 35) infections, as well as healthy Dutch individuals (n = 710) and humanized, recombinant anti-PGL-I IgM antibodies. Plot receiver operating characteristic curves were created and sensitivity (Sn), specificity (Sp) and the area under the curve were calculated to evaluate test performance.

Test results classified multibacillary leprosy patients with 95.0% Sn and 100% Sp using serum and 91.5% Sn and 99.8% Sp using FSB. Qualitative test results could be read after 2 min flow time, with accurate quantitation from 10 min onwards. The new anti-PGL-I IgM control supports production of batches with predetermined seropositivity thresholds and monitoring of the PGL-I QUR-test in various settings.

The operational version of the PGL-I QURapid with point-of-care applicability, meets the WHO target product profile criteria. Thus, this QUR-test is ready for public health implementations.