Background 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...Background 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 fiield-tested a lateral flow assay(LFA)quantitatively detecting human IgM against M./eprae-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).Methods 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),tubercu-losis(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.Results 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 seroposi-tivity thresholds and monitoring of the PGL-I QUR-test in various settings.Conclusion 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.展开更多
基金This study was made possible thanks to a grant from the Q.M.Gastmann-Wichers foundation(AG).
文摘Background 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 fiield-tested a lateral flow assay(LFA)quantitatively detecting human IgM against M./eprae-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).Methods 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),tubercu-losis(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.Results 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 seroposi-tivity thresholds and monitoring of the PGL-I QUR-test in various settings.Conclusion 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.
