Dataset Information

Prototype multi-biomarker test for point-of-care leprosy diagnostics.

ABSTRACT: To end the decade-long, obstinately stagnant number of new leprosy cases, there is an urgent need for field-applicable diagnostic tools that detect infection with Mycobacterium leprae, leprosy's etiologic agent. Since immunity against M. leprae is characterized by humoral and cellular markers, we developed a lateral flow test measuring multiple host proteins based on six previously identified biomarkers for various leprosy phenotypes. This multi-biomarker test (MBT) demonstrated feasibility of quantitative detection of six host serum proteins simultaneously, jointly allowing discrimination of patients with multibacillary and paucibacillary leprosy from control individuals in high and low leprosy endemic areas. Pilot testing of fingerstick blood showed similar MBT performance in point-of-care (POC) settings as observed for plasma and serum. Thus, this newly developed prototype MBT measures six biomarkers covering immunity against M. leprae across the leprosy spectrum. The MBT thereby provides the basis for immunodiagnostic POC tests for leprosy with potential for other (infectious) diseases as well.

SUBMITTER: van Hooij A

PROVIDER: S-EPMC7807156 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Prototype multi-biomarker test for point-of-care leprosy diagnostics.

van Hooij Anouk A Tjon Kon Fat Elisa M EM de Jong Danielle D Khatun Marufa M Soren Santosh S Chowdhury Abu Sufian AS Chandra Roy Johan J Alam Khorshed K Kim Jong-Pill JP Richardus Jan Hendrik JH Geluk Annemieke A Corstjens Paul L A M PLAM

iScience 20201229 1

To end the decade-long, obstinately stagnant number of new leprosy cases, there is an urgent need for field-applicable diagnostic tools that detect infection with <i>Mycobacterium leprae</i>, leprosy's etiologic agent. Since immunity against <i>M. leprae</i> is characterized by humoral and cellular markers, we developed a lateral flow test measuring multiple host proteins based on six previously identified biomarkers for various leprosy phenotypes. This multi-biomarker test (MBT) demonstrated fe ...[more]

PMID: 33490914

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Project description:BackgroundNucleic acid-based amplification tests (NAAT), above all (q)PCR, have been applied for the detection of Mycobacterium leprae in leprosy cases and household contacts with subclinical infection. However, their application in the field poses a range of technical challenges. Loop-mediated isothermal amplification (LAMP), as a promising point-of-care NAAT does not require sophisticated laboratory equipment, is easy to perform, and is applicable for decentralized diagnosis at the primary health care level. Among a range of gene targets, the M. leprae specific repetitive element RLEP is regarded as highly sensitive and specific for diagnostic applications. METHODS: Our group developed and validated a dry-reagent-based (DRB) RLEP LAMP, provided product specifications for customization of a ready-to-use kit (intended for commercial production) and compared it against the in-house prototype. The assays were optimized for application on a Genie® III portable fluorometer. For technical validation, 40 "must not detect RLEP" samples derived from RLEP qPCR negative exposed and non-exposed individuals, as well as from patients with other conditions and a set of closely related mycobacterial cultures, were tested together with 25 "must detect RLEP" samples derived from qPCR confirmed leprosy patients. For clinical validation, 150 RLEP qPCR tested samples were analyzed, consisting of the following categories: high-positive samples of multibacillary (MB) leprosy patients (> 10.000 bacilli/extract), medium-positive samples of MB leprosy patients (1.001-10.000 bacilli/extract), low-positive samples of MB leprosy patients (1-1.000 bacilli/extract), endemic controls and healthy non-exposed controls; each n = 30. RESULTS: Technical validation: both LAMP formats had a limit of detection of 1.000 RLEP copies, i.e. 43-27 bacilli, a sensitivity of 92% (in-house protocol)/100% (ready-to-use protocol) and a specificity of 100%. Reagents were stable for at least 1 year at 22 °C. Clinical validation: Both formats showed a negativity rate of 100% and a positivity rate of 100% for high-positive samples and 93-100% for medium positive samples, together with a positive predictive value of 100% and semi-quantitative results. The positivity rate for low-positive samples was 77% (in-house protocol)/43% (ready-to-use protocol) and differed significantly between both formats. CONCLUSIONS: The ready-to-use RLEP DRB LAMP assay constitutes an ASSURED test ready for field-based evaluation trials aiming for routine diagnosis of leprosy at the primary health care level.

Dataset Information

Prototype multi-biomarker test for point-of-care leprosy diagnostics.

Publications

Prototype multi-biomarker test for point-of-care leprosy diagnostics.

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