02633nas a2200253   4500000000100000008004100001100001200042700001200054700001600066700001500082700001300097700001400110700001200124700001300136700001100149700001600160700001700176700001600193700001200209245012700221856007200348520194500420022001402365       2019                            d1 aHooij A1 aEeden S1 aRichardus R1 aKon Fat ET1 aWilson L1 aFranken K1 aFaber R1 aKhatun M1 aAlam K1 aChowdhury A1 aRichardus JH1 aCorstjens P1 aGeluk A00aApplication of new host biomarker profiles in quantitative point-of-care tests facilitates leprosy diagnosis in the field.  uhttps://www.ebiomedicine.com/article/S2352-3964(19)30526-2/fulltext3 a<p><strong>BACKGROUND: </strong>Transmission of Mycobacterium leprae, the pathogen causing leprosy, is still persistent. To facilitate timely (prophylactic) treatment and reduce transmission it is vital to both early diagnose leprosy, and identify infected individuals lacking clinical symptoms. However, leprosy-specific biomarkers are limited, particularly for paucibacillary disease. Therefore, our objective was to identify new biomarkers for leprosy and assess their applicability in point-of-care (POC) tests.</p>

<p><strong>METHODS: </strong>Using multiplex-bead-arrays, 60 host-proteins were measured in a cross-sectional approach in 24-h whole blood assays (WBAs) collected in Bangladesh (79 patients; 54 contacts; 51 endemic controls (EC)). Next, 17 promising biomarkers were validated in WBAs of a separate cohort (55 patients; 27 EC). Finally, in a third cohort (36 patients; 20 EC), five candidate markers detectable in plasma were assessed for application in POC tests.</p>

<p><strong>FINDINGS: </strong>This study identified three new biomarkers for leprosy (ApoA1, IL-1Ra, S100A12), and confirmed five previously described biomarkers (CCL4, CRP, IL-10, IP-10, αPGL-I IgM). Overnight stimulation in WBAs provided increased specificity for leprosy and was required for IL-10, IL-1Ra and CCL4. The remaining five biomarkers were directly detectable in plasma, hence suitable for rapid POC tests. Indeed, lateral flow assays (LFAs) utilizing this five-marker profile detected both multi- and paucibacillary leprosy patients with variable immune responses.</p>

<p><strong>INTERPRETATION: </strong>Application of novel host-biomarker profiles to rapid, quantitative LFAs improves leprosy diagnosis and allows POC testing in low-resource settings. This platform can thus aid diagnosis and classification of leprosy and also provides a tool to detect M.leprae infection in large-scale contact screening in the field.</p>
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