Fingerstick test quantifying humoral and cellular biomarkers indicative for M. leprae infection

Corstjens, Paul L. A. M.; Hooij, Anouk van; Fat, Elisa M. Tjon Kon; Alam, Korshed; Vrolijk, Loes B.; Dlamini, Sipho; Silva, Moisés Batista da; Spencer, John S.; Salgado, Cláudio Guedes; Richardus, Jan Hendrik; Hees, C.L.M. van; Geluk, Annemieke

doi:10.1016/j.clinbiochem.2019.01.007

Cited by 29 publications

(34 citation statements)

References 52 publications

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“…In view of point-of-care (POC) test applicability (i.e. direct analysis of clinicals samples without antigen stimulation), biomarker levels were also assessed in plasma samples as a proxy for FSB collectable without venipuncture [3]. A plasma biomarker signature including αPGL-I IgM, IP-10, S100A12, ApoA1, CRP accurately detected leprosy patients irrespective of type with high sensitivity (86%) and specificity (90%) in the UCP-LFAs; indicating the diagnostic value of this signature in leprosy as it identifies both patients with high and low bacillary loads.…”

Section: Discussionmentioning

confidence: 99%

“…For discovery cohort and validation cohort I WBA samples, 4 ml venous blood was drawn and 1 ml applied directly to a microtube pre-coated with 10 μg M.leprae whole cell sonicate (WCS), 10 μg ML2478 and 10 μg ML0840 recombinant proteins (combined designated as Mlep) [3] or without stimulus (Med). Pre-coating of the tubes was done by lyophilizing the material.…”

Section: Methodsmentioning

confidence: 99%

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Application of new host biomarker profiles in quantitative point-of-care tests facilitates leprosy diagnosis in the field

et al. 2019

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BackgroundTransmission 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.MethodsUsing 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.FindingsThis 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.InterpretationApplication 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.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Application of new host biomarker profiles in quantitative point-of-care tests facilitates leprosy diagnosis in the field

et al. 2019

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“…Overall, over 200 recombinant proteins and peptides from M. leprae have been investigated as potential targets for serological and T cell-based diagnostic tests for M. leprae infection. Along those lines, two unique M. leprae proteins, ML2478 and ML0840, were shown to induce high IFN-γ responses in endemic control individuals from a high endemic country (Bangladesh) that were completely absent in control subjects from a nonendemic country (South Korea) [134,135]. Recently, fieldfriendly lateral flow assays have been developed that can simultaneously detect both humoral anti-PGL-I IgM responses and cell-mediated responses (IP-10, CCL4, and C-reactive protein [CRP]) to the recombinant ML2478/ML0840 proteins and a whole-cell sonicate.…”

Section: Diagnosis Of Leprosymentioning

confidence: 99%

“…Combined detection of all of these biomarkers significantly improved the diagnostic potential, particularly for PB leprosy in three endemic countries [135]. Simultaneous detection of anti-PGL-I IgM and cell-mediated biomarkers IP-10 and CRP was most recently tested using fingerstick blood to quantify humoral and cellular biomarkers indicative of M. leprae infection, allowing for a less invasive approach for the diagnosis of leprosy [135]. Longitudinal studies and additional validation of the newly developed RDTs are currently ongoing in different endemic and nonendemic countries.…”

Section: Diagnosis Of Leprosymentioning

confidence: 99%

The immunology of other mycobacteria: M. ulcerans, M. leprae

et al. 2020

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Mycobacterial pathogens can be categorized into three broad groups: Mycobacterium tuberculosis complex causing tuberculosis, M. leprae and M. lepromatosis causing leprosy, and atypical mycobacteria, or non-tuberculous mycobacteria (NTM), responsible for a wide range of diseases. Among the NTMs, M. ulcerans is responsible for the neglected tropical skin disease Buruli ulcer (BU). Most pathogenic mycobacteria, including M. leprae, evade effector mechanisms of the humoral immune system by hiding and replicating inside host cells and are furthermore excellent modulators of host immune responses. In contrast, M. ulcerans replicates predominantly extracellularly, sheltered from host immune responses through the cytotoxic and immunosuppressive effects of mycolactone, a macrolide produced by the bacteria. In the year 2018, 208,613 new cases of leprosy and 2713 new cases of BU were reported to WHO, figures which are notoriously skewed by vast underreporting of these diseases.

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“…Because a diagnosis of leprosy is usually made on clinical signs and symptoms and there is no “gold standard” nor easy method to correlate infection to disease progression, patients are often diagnosed and treated late, increasing the likelihood of further transmission and disease-related disability. Contact screening may offer opportunities for early diagnosis [ 18 , 19 ] and targeted interventions. Another priority is harmonization, i.e., validation and quality assurance programmes to ensure standard procedures, correct interpretation, and thus high confidence in test results [ 20 ].…”

Section: Panel: the Research Priorities To Achieve Zero Leprosymentioning

confidence: 99%

A comprehensive research agenda for zero leprosy

et al. 2020

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Background Leprosy control achieved dramatic success in the 1980s–1990s with the implementation of short course multidrug therapy, which reduced the global prevalence of leprosy to less than 1 in 10 000 population. However, a period of relative stagnation in leprosy control followed this achievement, and only limited further declines in the global number of new cases reported have been achieved over the past decade. Main text In 2016, major stakeholders called for the development of an innovative and comprehensive leprosy strategy aimed at reducing the incidence of leprosy, lowering the burden of disability and discrimination, and interrupting transmission. This led to the establishment of the Global Partnership for Zero Leprosy (GPZL) in 2018, with partners aligned around a shared Action Framework committed to achieving the WHO targets by 2030 through national leprosy program capacity-building, resource mobilisation and an enabling research agenda. GPZL convened over 140 experts from more than 20 countries to develop a research agenda to achieve zero leprosy. The result is a detailed research agenda focusing on diagnostics, mapping, digital technology and innovation, disability, epidemiological modelling and investment case, implementation research, stigma, post exposure prophylaxis and transmission, and vaccines. This research agenda is aligned with the research priorities identified by other stakeholders. Conclusions Developing and achieving consensus on the research agenda for zero leprosy is a significant step forward for the leprosy community. In a next step, research programmes must be developed, with individual components of the research agenda requiring distinct expertise, varying in resource needs, and operating over different timescales. Moving toward zero leprosy now requires partner alignment and new investments at all stages of the research process, from discovery to implementation.

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Fingerstick test quantifying humoral and cellular biomarkers indicative for M. leprae infection

Cited by 29 publications

References 52 publications

Application of new host biomarker profiles in quantitative point-of-care tests facilitates leprosy diagnosis in the field

Application of new host biomarker profiles in quantitative point-of-care tests facilitates leprosy diagnosis in the field

The immunology of other mycobacteria: M. ulcerans, M. leprae

A comprehensive research agenda for zero leprosy

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