Paul L A M Corstjens1, Anouk van Hooij2, Elisa M Tjon Kon Fat1, Korshed Alam3, Loes B Vrolijk4, Sipho Dlamini5, Moises Batista da Silva6, John S Spencer7, Claudio G Salgado6, Jan Hendrik Richardus8, Colette L M van Hees9, Annemieke Geluk10. 1. Dept. Cell and Chemical Biology, Leiden University Medical Center, The Netherlands. 2. Dept. of Infectious Diseases, Leiden University Medical Center, The Netherlands. 3. Rural Health Program, The Leprosy Mission International Bangladesh, Nilphamari, Bangladesh. 4. Dept. of Infectious Diseases, Leiden University Medical Center, The Netherlands; Division of Dermatology, New Groote Schuur Hospital, Cape Town, South Africa. 5. Division of Dermatology, New Groote Schuur Hospital, Cape Town, South Africa. 6. Laboratório de Dermato-Imunologia, Instituto de Ciências Biológicas, Universidade Federal do Pará, Marituba, Pará, Brazil. 7. Dept. of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, USA. 8. Dept. of Public Health, Erasmus MC, University Medical Center Rotterdam, The Netherlands. 9. Dept. of Dermatology, Erasmus MC, University Medical Center Rotterdam, The Netherlands. 10. Dept. of Infectious Diseases, Leiden University Medical Center, The Netherlands. Electronic address: a.geluk@lumc.nl.
Abstract
OBJECTIVES: New user-friendly diagnostic tests for detection of individuals infected by Mycobacterium leprae (M. leprae), the causative pathogen of leprosy, can help guide therapeutic and prophylactic treatment, thus positively contributing to clinical outcome and reduction of transmission. To facilitate point-of-care testing without the presence of phlebotomists, the use of fingerstick blood (FSB) rather than whole blood-derived serum is preferred. This study is a first proof-of-principle validating that previously described rapid serum tests detecting antibodies and cytokines can also be used with FSB. METHODS: Quantitative detection of previously identified biomarkers for leprosy and M. leprae infection, anti-M. leprae PGL-I IgM antibodies (αPGL-I), IP-10 and CRP, was performed with lateral flow (LF) strips utilizing luminescent up-converting reporter particles (UCP) and a portable reader generating unbiased read-outs. Precise amounts of FSB samples were collected using disposable heparinized capillaries. Biomarker levels in paired FSB and serum samples were determined using UCP-LF test strips for leprosy patients and controls in Bangladesh, Brazil, South-Africa and the Netherlands. RESULTS: Correlations between serum and FSB from the same individuals for αPGL-I, CRP and IP-10 were highly significant (p < .0001) even after FSB samples had been frozen. The αPGL-I FSB test was able to correctly identify all multibacillary leprosy patients presenting a good quantitative correlation with the bacterial index. CONCLUSIONS: Reader-assisted, quantitative UCP-LF tests for the detection of humoral and cellular biomarkers for M. leprae infection, are compatible with FSB. This allows near-patient testing for M. leprae infection and immunomonitoring of treatment without highly trained staff. On site availability of test-result concedes immediate initiation of appropriate counselling and treatment. Alternatively, the UCP-LF format allows frozen storage of FSB samples compatible with deferred testing in central laboratories.
OBJECTIVES: New user-friendly diagnostic tests for detection of individuals infected by Mycobacterium leprae (M. leprae), the causative pathogen of leprosy, can help guide therapeutic and prophylactic treatment, thus positively contributing to clinical outcome and reduction of transmission. To facilitate point-of-care testing without the presence of phlebotomists, the use of fingerstick blood (FSB) rather than whole blood-derived serum is preferred. This study is a first proof-of-principle validating that previously described rapid serum tests detecting antibodies and cytokines can also be used with FSB. METHODS: Quantitative detection of previously identified biomarkers for leprosy and M. leprae infection, anti-M. leprae PGL-I IgM antibodies (αPGL-I), IP-10 and CRP, was performed with lateral flow (LF) strips utilizing luminescent up-converting reporter particles (UCP) and a portable reader generating unbiased read-outs. Precise amounts of FSB samples were collected using disposable heparinized capillaries. Biomarker levels in paired FSB and serum samples were determined using UCP-LF test strips for leprosypatients and controls in Bangladesh, Brazil, South-Africa and the Netherlands. RESULTS: Correlations between serum and FSB from the same individuals for αPGL-I, CRP and IP-10 were highly significant (p < .0001) even after FSB samples had been frozen. The αPGL-I FSB test was able to correctly identify all multibacillary leprosypatients presenting a good quantitative correlation with the bacterial index. CONCLUSIONS: Reader-assisted, quantitative UCP-LF tests for the detection of humoral and cellular biomarkers for M. leprae infection, are compatible with FSB. This allows near-patient testing for M. leprae infection and immunomonitoring of treatment without highly trained staff. On site availability of test-result concedes immediate initiation of appropriate counselling and treatment. Alternatively, the UCP-LF format allows frozen storage of FSB samples compatible with deferred testing in central laboratories.
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