Background:Early detection and treatment of neuropathy in leprosy is important to prevent disabilities.A recent study showed that the Nerve Conduction Studies(NCS)and Warm Detection Thresholds(WDT)tests can detect lep...Background:Early detection and treatment of neuropathy in leprosy is important to prevent disabilities.A recent study showed that the Nerve Conduction Studies(NCS)and Warm Detection Thresholds(WDT)tests can detect leprosy neuropathy the earliest.These two tests are not practical under field conditions,however,because they require climate-controlled rooms and highly trained staff and are expensive.We assessed the usefulness of alternative test methods and their sensitivity and specificity to detect neuropathy at an early stage.Methods:Through a literature search we identified five alternative devices that appeared user-friendly,more affordable,portable and/or battery-operated:the Neuropad^(■),Vibratip^(TM),NC-Stat^(■)DPNCheck^(TM),NeuroQuick and the Thermal Sensibility Tester(TST),assessing respectively sweat function,vibration sensation,nerve conduction,cold sensation and warm sensation.In leprosy patients in Bangladesh,the posterior tibial and sural nerves that tested normal for the monofilament test and voluntary muscle test were assessed with the NCS and WDT as reference standard tests.The alternative devices were then tested on 94 nerves with abnormal WDT and/or NCS results and on 94 unaffected nerves.Sensitivity and specificity were the main outcomes.Results:The NeuroQuick and the TST showed very good sensitivity and specificity.On the sural nerve,the NeuroQuick had both a sensitivity and a specificity of 86%.The TST had a sensitivity of 83%and a specificity of 82%.Both the NC-Stat^(■)DPNCheck^(TM)and Vibratip^(TM)had a high specificity(88%and 100%),but a low sensitivity(16%and 0%).On the posterior tibial nerve,the NeuroQuick and the TST also showed good sensitivity,but the sensitivity was lower than for the sural nerve.The Neuropad^(■)had a sensitivity of 56%and a specificity of 61%.Conclusions:The NeuroQuick and TST are good candidates for further field-testing for reliability and reproducibility.The feasibility of production on a larger scale should be examined.展开更多
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The study was a sub-study of the TENLEP trial.The TENLEP trial was funded by the The American Leprosy Mission,the German Leprosy and TB Relief Association,the Netherlands Leprosy Relief,the Ordre de Malte,and the Turing Foundation.
文摘Background:Early detection and treatment of neuropathy in leprosy is important to prevent disabilities.A recent study showed that the Nerve Conduction Studies(NCS)and Warm Detection Thresholds(WDT)tests can detect leprosy neuropathy the earliest.These two tests are not practical under field conditions,however,because they require climate-controlled rooms and highly trained staff and are expensive.We assessed the usefulness of alternative test methods and their sensitivity and specificity to detect neuropathy at an early stage.Methods:Through a literature search we identified five alternative devices that appeared user-friendly,more affordable,portable and/or battery-operated:the Neuropad^(■),Vibratip^(TM),NC-Stat^(■)DPNCheck^(TM),NeuroQuick and the Thermal Sensibility Tester(TST),assessing respectively sweat function,vibration sensation,nerve conduction,cold sensation and warm sensation.In leprosy patients in Bangladesh,the posterior tibial and sural nerves that tested normal for the monofilament test and voluntary muscle test were assessed with the NCS and WDT as reference standard tests.The alternative devices were then tested on 94 nerves with abnormal WDT and/or NCS results and on 94 unaffected nerves.Sensitivity and specificity were the main outcomes.Results:The NeuroQuick and the TST showed very good sensitivity and specificity.On the sural nerve,the NeuroQuick had both a sensitivity and a specificity of 86%.The TST had a sensitivity of 83%and a specificity of 82%.Both the NC-Stat^(■)DPNCheck^(TM)and Vibratip^(TM)had a high specificity(88%and 100%),but a low sensitivity(16%and 0%).On the posterior tibial nerve,the NeuroQuick and the TST also showed good sensitivity,but the sensitivity was lower than for the sural nerve.The Neuropad^(■)had a sensitivity of 56%and a specificity of 61%.Conclusions:The NeuroQuick and TST are good candidates for further field-testing for reliability and reproducibility.The feasibility of production on a larger scale should be examined.
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.
