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dc.contributor.author | Roberts, Adam J | |
dc.contributor.author | Ong, Han Boon | |
dc.contributor.author | Clare, Simon | |
dc.contributor.author | Brandt, Cordelia | |
dc.contributor.author | Harcourt, Katherine | |
dc.contributor.author | Takele, Yegnasew | |
dc.contributor.author | Ghosh, Prakash | |
dc.contributor.author | Toepp, Angela | |
dc.contributor.author | Waugh, Max | |
dc.contributor.author | Matano, Daniel | |
dc.contributor.author | Färnert, Anna | |
dc.contributor.author | Adams, Emily | |
dc.contributor.author | Moreno, Javier | |
dc.contributor.author | Mbuchi, Margaret | |
dc.contributor.author | Petersen, Christine | |
dc.contributor.author | Mondal, Dinesh | |
dc.contributor.author | Kropf, Pascale | |
dc.contributor.author | Wright, Gavin J | |
dc.date.accessioned | 2024-07-02T11:24:30Z | |
dc.date.available | 2024-07-02T11:24:30Z | |
dc.date.issued | 2024-05-08 | |
dc.identifier.citation | mBio. 2024 May 8;15(5):e0085924. | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/19905 | |
dc.description.abstract | Visceral leishmaniasis is a deadly infectious disease and is one of the world's major neglected health problems. Because the symptoms of infection are similar to other endemic diseases, accurate diagnosis is crucial for appropriate treatment. Definitive diagnosis using splenic or bone marrow aspirates is highly invasive, and so, serological assays are preferred, including the direct agglutination test (DAT) or rK39 strip test. These tests, however, are either difficult to perform in the field (DAT) or lack specificity in some endemic regions (rK39), making the development of new tests a research priority. The availability of Leishmania spp. genomes presents an opportunity to identify new diagnostic targets. Here, we use genome data and a mammalian protein expression system to create a panel of 93 proteins consisting of the extracellular ectodomains of the Leishmania donovani cell surface and secreted proteins. We use these panel and sera from murine experimental infection models and natural human and canine infections to identify new candidates for serological diagnosis. We observed a concordance between the most immunoreactive antigens in different host species and transmission settings. The antigen encoded by the LdBPK_323600.1 gene can diagnose Leishmania infections with high sensitivity and specificity in patient cohorts from different endemic regions including Bangladesh and Ethiopia. In longitudinal sampling of treated patients, we observed reductions in immunoreactivity to LdBPK_323600.1 suggesting it could be used to diagnose treatment success. In summary, we have identified new antigens that could contribute to improved serological diagnostic tests to help control the impact of this deadly tropical infectious disease. IMPORTANCE Visceral leishmaniasis is fatal if left untreated with patients often displaying mild and non-specific symptoms during the early stages of infection making accurate diagnosis important. Current methods for diagnosis require highly trained medical staff to perform highly invasive biopsies of the liver or bone marrow which pose risks to the patient. Less invasive molecular tests are available but can suffer from regional variations in their ability to accurately diagnose an infection. To identify new diagnostic markers of visceral leishmaniasis, we produced and tested a panel of 93 proteins identified from the genome of the parasite responsible for this disease. We found that the pattern of host antibody reactivity to these proteins was broadly consistent across naturally acquired infections in both human patients and dogs, as well as experimental rodent infections. We identified a new protein called LdBPK_323600.1 that could accurately diagnose visceral leishmaniasis infections in humans. | es_ES |
dc.description.sponsorship | This work was funded by the Wellcome Trust (grant 206194) and EDCTP (grant RIA2020I-3290, “VL INNO”). The Kenyan sample collection was supported through funding from the Foundation for Innovative New Diagnostics (FIND) to Margaret Mbuchi (grant LE14-0016); this work has been published with permission from the Director of KEMRI. The Bangladesh sample collection was supported through funding from the Foundation for Innovative New Diagnostics (FIND) to Dinesh Mondal, and ICDRRB (LE15-0007) and LSTM support for this project was provided by Wellcome Trust Seed Fund made to Emily Adams (108080/Z/15/Z). Sample collection from Ethiopia was funded by a Wellcome Trust Training Fellowship in Public Health and Tropical Medicine (204797/Z/16/Z). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The views expressed by the authors do not necessarily reflect the views of the funding agencies. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | American Society for Microbiology (ASM) | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | Serology | es_ES |
dc.subject | Proteins | es_ES |
dc.subject | Visceral leishmaniasis | es_ES |
dc.subject | ELISA | es_ES |
dc.subject | Leishmania donovani | es_ES |
dc.subject | Recombinant proteins | es_ES |
dc.subject.mesh | Leishmania donovani | es_ES |
dc.subject.mesh | Leishmaniasis, Visceral | es_ES |
dc.subject.mesh | Antigens, Protozoan | es_ES |
dc.subject.mesh | Antibodies, Protozoan | es_ES |
dc.subject.mesh | Protozoan Proteins | es_ES |
dc.subject.mesh | Serologic Tests | es_ES |
dc.subject.mesh | Animals | es_ES |
dc.subject.mesh | Humans | es_ES |
dc.subject.mesh | Mice | es_ES |
dc.subject.mesh | Dogs | es_ES |
dc.subject.mesh | Biomarkers | es_ES |
dc.subject.mesh | Female | es_ES |
dc.subject.mesh | Recombinant Proteins | es_ES |
dc.subject.mesh | Mice, Inbred BALB C | es_ES |
dc.subject.mesh | Membrane Proteins | es_ES |
dc.subject.mesh | Sensitivity and Specificity | es_ES |
dc.subject.mesh | Dog Diseases | es_ES |
dc.title | A panel of recombinant Leishmania donovani cell surface and secreted proteins identifies LdBPK_323600.1 as a serological marker of symptomatic infection | es_ES |
dc.type | research article | es_ES |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.identifier.pubmedID | 38639536 | es_ES |
dc.format.volume | 15 | es_ES |
dc.format.number | 5 | es_ES |
dc.format.page | e0085924 | es_ES |
dc.identifier.doi | 10.1128/mbio.00859-24 | es_ES |
dc.contributor.funder | Wellcome Trust | es_ES |
dc.contributor.funder | Unión Europea. Comisión Europea. H2020 | es_ES |
dc.contributor.funder | Foundation for Innovative New Diagnostics (Suiza) | es_ES |
dc.contributor.funder | European and Developing Countries Clinical Trials Partnership (EDCTP) | es_ES |
dc.contributor.funder | Unión Europea. Comisión Europea. Horizonte Europa. ERA-LEARN | es_ES |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 2150-7511 | es_ES |
dc.relation.publisherversion | https://doi.org/10.1128/mbio.00859-24 | es_ES |
dc.identifier.journal | mBio | es_ES |
dc.repisalud.centro | ISCIII::Centro Nacional de Microbiología | es_ES |
dc.repisalud.institucion | ISCIII | es_ES |
dc.rights.accessRights | open access | es_ES |