Longitudinal study of cross-reactive antigenemia in individuals with high Loa loa microfilarial density reveals promising biomarkers for distinguishing lymphatic filariasis from loiasis
Background and methodsCirculating Loa loa antigens are often detected in individuals with heavy L. loa infections by diagnostic tests for lymphatic filariasis (LF) caused by Wuchereria bancrofti. This is a major challenge to LF mapping and elimination efforts in loiasis co-endemic areas. However, it...
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Frontiers Media S.A.
2023-11-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fpara.2023.1292837/full |
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author | Linda Djune-Yemeli Linda Djune-Yemeli Marla Hertz Hugues C. Nana-Djeunga Amy Rush Petra Erdmann-Gilmore Robert Sprung Jean Gabin Bopda Reid Townsend Palmer Masumbe Netongo Palmer Masumbe Netongo Joseph Kamgno Joseph Kamgno Philip J. Budge |
author_facet | Linda Djune-Yemeli Linda Djune-Yemeli Marla Hertz Hugues C. Nana-Djeunga Amy Rush Petra Erdmann-Gilmore Robert Sprung Jean Gabin Bopda Reid Townsend Palmer Masumbe Netongo Palmer Masumbe Netongo Joseph Kamgno Joseph Kamgno Philip J. Budge |
author_sort | Linda Djune-Yemeli |
collection | DOAJ |
description | Background and methodsCirculating Loa loa antigens are often detected in individuals with heavy L. loa infections by diagnostic tests for lymphatic filariasis (LF) caused by Wuchereria bancrofti. This is a major challenge to LF mapping and elimination efforts in loiasis co-endemic areas. However, it also provides an opportunity to identify antigen biomarkers for loiasis. To determine which L. loa antigens might be promising biomarkers for distinguishing true LF from loiasis, we screened for L. loa antigens in a group of individuals with heavy L. loa infections living in the Okola Health District of Cameroon. In this longitudinal study, participants were tested for cross-reactive antigenemia by filariasis test strip (FTS), ELISA, and western blot, and were monitored for FTS status at 6, 9, 12, and 15 months post-enrollment. We then identified specific circulating L. loa antigens by liquid chromatography-tandem mass spectrometry (LC-MS/MS) from baseline and 15-month plasma samples.Principal findings and conclusionsAmong 73 FTS-positive (FTS+) and 13 FTS-negative (FTS-) participants with high L. loa microfilarial loads, 83% maintained their FTS status over the course of the study, while 17% experienced at least one FTS conversion event (from FTS+ to FTS- or vice versa). Cross-reactive antigens were detected in both FTS+ and FTS- sera by western blot, and there was poor agreement in antigen detection by FTS, western blot, and ELISA methods. One protein family, a group of Nas-14 metalloproteases, was detected by LC MS/MS in >80% of tested samples, including FTS- samples. These data identify Nas-14 as a promising loiasis biomarker potentially capable of distinguishing loiasis from lymphatic filariasis. |
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language | English |
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spelling | doaj.art-0588a95841d44a9baa974eee7f52664a2023-11-18T10:09:18ZengFrontiers Media S.A.Frontiers in Parasitology2813-24242023-11-01210.3389/fpara.2023.12928371292837Longitudinal study of cross-reactive antigenemia in individuals with high Loa loa microfilarial density reveals promising biomarkers for distinguishing lymphatic filariasis from loiasisLinda Djune-Yemeli0Linda Djune-Yemeli1Marla Hertz2Hugues C. Nana-Djeunga3Amy Rush4Petra Erdmann-Gilmore5Robert Sprung6Jean Gabin Bopda7Reid Townsend8Palmer Masumbe Netongo9Palmer Masumbe Netongo10Joseph Kamgno11Joseph Kamgno12Philip J. Budge13Higher Institute of Scientific and Medical Research (ISM), Yaoundé, CameroonMolecular Diagnostics Research Group, Biotechnology Centre-University of Yaoundé I (BTC-UY-I), Yaoundé, CameroonOffice of Scholarly Communication, University of Alabama at Birmingham Libraries, Birmingham, AL, United StatesHigher Institute of Scientific and Medical Research (ISM), Yaoundé, CameroonInfectious Disease Division, Department of Medicine, Washington University in St. Louis, St. Louis, MO, United StatesDivision of Endocrinology, Metabolism and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, MO, United StatesDivision of Endocrinology, Metabolism and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, MO, United StatesHigher Institute of Scientific and Medical Research (ISM), Yaoundé, CameroonDivision of Endocrinology, Metabolism and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, MO, United StatesMolecular Diagnostics Research Group, Biotechnology Centre-University of Yaoundé I (BTC-UY-I), Yaoundé, CameroonDepartement of Biochemistry, Faculty of Sciences, University of Yaoundé I, Yaoundé, CameroonHigher Institute of Scientific and Medical Research (ISM), Yaoundé, CameroonFaculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, CameroonInfectious Disease Division, Department of Medicine, Washington University in St. Louis, St. Louis, MO, United StatesBackground and methodsCirculating Loa loa antigens are often detected in individuals with heavy L. loa infections by diagnostic tests for lymphatic filariasis (LF) caused by Wuchereria bancrofti. This is a major challenge to LF mapping and elimination efforts in loiasis co-endemic areas. However, it also provides an opportunity to identify antigen biomarkers for loiasis. To determine which L. loa antigens might be promising biomarkers for distinguishing true LF from loiasis, we screened for L. loa antigens in a group of individuals with heavy L. loa infections living in the Okola Health District of Cameroon. In this longitudinal study, participants were tested for cross-reactive antigenemia by filariasis test strip (FTS), ELISA, and western blot, and were monitored for FTS status at 6, 9, 12, and 15 months post-enrollment. We then identified specific circulating L. loa antigens by liquid chromatography-tandem mass spectrometry (LC-MS/MS) from baseline and 15-month plasma samples.Principal findings and conclusionsAmong 73 FTS-positive (FTS+) and 13 FTS-negative (FTS-) participants with high L. loa microfilarial loads, 83% maintained their FTS status over the course of the study, while 17% experienced at least one FTS conversion event (from FTS+ to FTS- or vice versa). Cross-reactive antigens were detected in both FTS+ and FTS- sera by western blot, and there was poor agreement in antigen detection by FTS, western blot, and ELISA methods. One protein family, a group of Nas-14 metalloproteases, was detected by LC MS/MS in >80% of tested samples, including FTS- samples. These data identify Nas-14 as a promising loiasis biomarker potentially capable of distinguishing loiasis from lymphatic filariasis.https://www.frontiersin.org/articles/10.3389/fpara.2023.1292837/fullLoiasislymphatic filariasiscross-reactivityLF-rapid diagnostic testsbiomarker |
spellingShingle | Linda Djune-Yemeli Linda Djune-Yemeli Marla Hertz Hugues C. Nana-Djeunga Amy Rush Petra Erdmann-Gilmore Robert Sprung Jean Gabin Bopda Reid Townsend Palmer Masumbe Netongo Palmer Masumbe Netongo Joseph Kamgno Joseph Kamgno Philip J. Budge Longitudinal study of cross-reactive antigenemia in individuals with high Loa loa microfilarial density reveals promising biomarkers for distinguishing lymphatic filariasis from loiasis Frontiers in Parasitology Loiasis lymphatic filariasis cross-reactivity LF-rapid diagnostic tests biomarker |
title | Longitudinal study of cross-reactive antigenemia in individuals with high Loa loa microfilarial density reveals promising biomarkers for distinguishing lymphatic filariasis from loiasis |
title_full | Longitudinal study of cross-reactive antigenemia in individuals with high Loa loa microfilarial density reveals promising biomarkers for distinguishing lymphatic filariasis from loiasis |
title_fullStr | Longitudinal study of cross-reactive antigenemia in individuals with high Loa loa microfilarial density reveals promising biomarkers for distinguishing lymphatic filariasis from loiasis |
title_full_unstemmed | Longitudinal study of cross-reactive antigenemia in individuals with high Loa loa microfilarial density reveals promising biomarkers for distinguishing lymphatic filariasis from loiasis |
title_short | Longitudinal study of cross-reactive antigenemia in individuals with high Loa loa microfilarial density reveals promising biomarkers for distinguishing lymphatic filariasis from loiasis |
title_sort | longitudinal study of cross reactive antigenemia in individuals with high loa loa microfilarial density reveals promising biomarkers for distinguishing lymphatic filariasis from loiasis |
topic | Loiasis lymphatic filariasis cross-reactivity LF-rapid diagnostic tests biomarker |
url | https://www.frontiersin.org/articles/10.3389/fpara.2023.1292837/full |
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