8 research outputs found

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

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    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.Cancer Signaling networks and Molecular Therapeutic

    Rhesus macaques self-curing from a schistosome infection can display complete immunity to challenge

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    To date there is only one single drug with modest efficacy and no vaccine available to protect from schistosomiasis. Here, Amaral et al. characterize the self-cure process of rhesus macaques following primary infection and secondary challenge with Schistosoma mansoni to inform future vaccine development studies.The rhesus macaque provides a unique model of acquired immunity against schistosomes, which afflict >200 million people worldwide. By monitoring bloodstream levels of parasite-gut-derived antigen, we show that from week 10 onwards an established infection with Schistosoma mansoni is cleared in an exponential manner, eliciting resistance to reinfection. Secondary challenge at week 42 demonstrates that protection is strong in all animals and complete in some. Antibody profiles suggest that antigens mediating protection are the released products of developing schistosomula. In culture they are killed by addition of rhesus plasma, collected from week 8 post-infection onwards, and even more efficiently with post-challenge plasma. Furthermore, cultured schistosomula lose chromatin activating marks at the transcription start site of genes related to worm development and show decreased expression of genes related to lysosomes and lytic vacuoles involved with autophagy. Overall, our results indicate that enhanced antibody responses against the challenge migrating larvae mediate the naturally acquired protective immunity and will inform the route to an effective vaccine.Cancer Signaling networks and Molecular Therapeutic

    Field-Friendly Test for Monitoring Multiple Immune Response Markers during Onset and Treatment of Exacerbated Immunity in Leprosy

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    Acute inflammatory reactions represent the major cause of irreversible neuropathy in leprosy. These tissue-destroying episodes have considerable overlap with acute immunological complications (flares) in several chronic (autoimmune) diseases that similarly warrant early detection. However, the lack of diagnostic tests impedes early diagnosis of these reactions. Here, we evaluated a user-friendly multiplex lateral flow assay for the simultaneous detection of IP-10 and anti-phenolic glycolipid I antibodies for longitudinally monitoring early onset and treatment of leprosy reactions.Immunogenetics and cellular immunology of bacterial infectious disease
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