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...

Full description

Bibliographic Details
Main Authors: Linda Djune-Yemeli, Marla Hertz, Hugues C. Nana-Djeunga, Amy Rush, Petra Erdmann-Gilmore, Robert Sprung, Jean Gabin Bopda, Reid Townsend, Palmer Masumbe Netongo, Joseph Kamgno, Philip J. Budge
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-11-01
Series:Frontiers in Parasitology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fpara.2023.1292837/full
_version_ 1797595079613874176
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.
first_indexed 2024-03-11T02:32:20Z
format Article
id doaj.art-0588a95841d44a9baa974eee7f52664a
institution Directory Open Access Journal
issn 2813-2424
language English
last_indexed 2024-03-11T02:32:20Z
publishDate 2023-11-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Parasitology
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
work_keys_str_mv AT lindadjuneyemeli longitudinalstudyofcrossreactiveantigenemiainindividualswithhighloaloamicrofilarialdensityrevealspromisingbiomarkersfordistinguishinglymphaticfilariasisfromloiasis
AT lindadjuneyemeli longitudinalstudyofcrossreactiveantigenemiainindividualswithhighloaloamicrofilarialdensityrevealspromisingbiomarkersfordistinguishinglymphaticfilariasisfromloiasis
AT marlahertz longitudinalstudyofcrossreactiveantigenemiainindividualswithhighloaloamicrofilarialdensityrevealspromisingbiomarkersfordistinguishinglymphaticfilariasisfromloiasis
AT huguescnanadjeunga longitudinalstudyofcrossreactiveantigenemiainindividualswithhighloaloamicrofilarialdensityrevealspromisingbiomarkersfordistinguishinglymphaticfilariasisfromloiasis
AT amyrush longitudinalstudyofcrossreactiveantigenemiainindividualswithhighloaloamicrofilarialdensityrevealspromisingbiomarkersfordistinguishinglymphaticfilariasisfromloiasis
AT petraerdmanngilmore longitudinalstudyofcrossreactiveantigenemiainindividualswithhighloaloamicrofilarialdensityrevealspromisingbiomarkersfordistinguishinglymphaticfilariasisfromloiasis
AT robertsprung longitudinalstudyofcrossreactiveantigenemiainindividualswithhighloaloamicrofilarialdensityrevealspromisingbiomarkersfordistinguishinglymphaticfilariasisfromloiasis
AT jeangabinbopda longitudinalstudyofcrossreactiveantigenemiainindividualswithhighloaloamicrofilarialdensityrevealspromisingbiomarkersfordistinguishinglymphaticfilariasisfromloiasis
AT reidtownsend longitudinalstudyofcrossreactiveantigenemiainindividualswithhighloaloamicrofilarialdensityrevealspromisingbiomarkersfordistinguishinglymphaticfilariasisfromloiasis
AT palmermasumbenetongo longitudinalstudyofcrossreactiveantigenemiainindividualswithhighloaloamicrofilarialdensityrevealspromisingbiomarkersfordistinguishinglymphaticfilariasisfromloiasis
AT palmermasumbenetongo longitudinalstudyofcrossreactiveantigenemiainindividualswithhighloaloamicrofilarialdensityrevealspromisingbiomarkersfordistinguishinglymphaticfilariasisfromloiasis
AT josephkamgno longitudinalstudyofcrossreactiveantigenemiainindividualswithhighloaloamicrofilarialdensityrevealspromisingbiomarkersfordistinguishinglymphaticfilariasisfromloiasis
AT josephkamgno longitudinalstudyofcrossreactiveantigenemiainindividualswithhighloaloamicrofilarialdensityrevealspromisingbiomarkersfordistinguishinglymphaticfilariasisfromloiasis
AT philipjbudge longitudinalstudyofcrossreactiveantigenemiainindividualswithhighloaloamicrofilarialdensityrevealspromisingbiomarkersfordistinguishinglymphaticfilariasisfromloiasis