IgG1 as a potential biomarker of post-chemotherapeutic relapse in visceral leishmaniasis, and adaptation to a rapid diagnostic test.
BACKGROUND: Visceral leishmaniasis (VL), caused by protozoa of the Leishmania donovani complex, is a widespread parasitic disease of great public health importance; without effective chemotherapy symptomatic VL is usually fatal. Distinction of asymptomatic carriage from progressive disease and the p...
Published in: | PLoS Neglected Tropical Diseases |
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Online Access: | https://doi.org/10.1371/journal.pntd.0003273 https://doaj.org/article/478f2acb1fec4ec7a5db4327c5ceac98 |
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ftdoajarticles:oai:doaj.org/article:478f2acb1fec4ec7a5db4327c5ceac98 2023-05-15T15:14:46+02:00 IgG1 as a potential biomarker of post-chemotherapeutic relapse in visceral leishmaniasis, and adaptation to a rapid diagnostic test. Tapan Bhattacharyya Armon Ayandeh Andrew K Falconar Shyam Sundar Sayda El-Safi Marissa A Gripenberg Duncan E Bowes Caroline Thunissen Om Prakash Singh Rajiv Kumar Osman Ahmed Osama Eisa Alfarazdeg Saad Sara Silva Pereira Marleen Boelaert Pascal Mertens Michael A Miles 2014-10-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0003273 https://doaj.org/article/478f2acb1fec4ec7a5db4327c5ceac98 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC4207679?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0003273 https://doaj.org/article/478f2acb1fec4ec7a5db4327c5ceac98 PLoS Neglected Tropical Diseases, Vol 8, Iss 10, p e3273 (2014) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2014 ftdoajarticles https://doi.org/10.1371/journal.pntd.0003273 2022-12-31T14:13:26Z BACKGROUND: Visceral leishmaniasis (VL), caused by protozoa of the Leishmania donovani complex, is a widespread parasitic disease of great public health importance; without effective chemotherapy symptomatic VL is usually fatal. Distinction of asymptomatic carriage from progressive disease and the prediction of relapse following treatment are hampered by the lack of prognostic biomarkers for use at point of care. METHODOLOGY/PRINCIPAL FINDINGS: All IgG subclass and IgG isotype antibody levels were determined using unpaired serum samples from Indian and Sudanese patients with differing clinical status of VL, which included pre-treatment active VL, post-treatment cured, post-treatment relapsed, and post kala-azar dermal leishmaniasis (PKDL), as well as seropositive (DAT and/or rK39) endemic healthy controls (EHCs) and seronegative EHCs. L. donovani antigen-specific IgG1 levels were significantly elevated in relapsed versus cured VL patients (p<0.0001). Using paired Indian VL sera, consistent with the known IgG1 half-life, IgG1 levels had not decreased significantly at day 30 after the start of treatment (p = 0.8304), but were dramatically decreased by 6 months compared to day 0 (p = 0.0032) or day 15 (p<0.0001) after start of treatment. Similarly, Sudanese sera taken soon after treatment did not show a significant change in the IgG1 levels (p = 0.3939). Two prototype lateral flow immunochromatographic rapid diagnostic tests (RDTs) were developed to detect IgG1 levels following VL treatment: more than 80% of the relapsed VL patients were IgG1 positive; at least 80% of the cured VL patients were IgG1 negative (p<0.0001). CONCLUSIONS/SIGNIFICANCE: Six months after treatment of active VL, elevated levels of specific IgG1 were associated with treatment failure and relapse, whereas no IgG1 or low levels were detected in cured VL patients. A lateral flow RDT was successfully developed to detect anti-Leishmania IgG1 as a potential biomarker of post-chemotherapeutic relapse. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Azar ENVELOPE(-63.733,-63.733,-64.983,-64.983) Indian PLoS Neglected Tropical Diseases 8 10 e3273 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Tapan Bhattacharyya Armon Ayandeh Andrew K Falconar Shyam Sundar Sayda El-Safi Marissa A Gripenberg Duncan E Bowes Caroline Thunissen Om Prakash Singh Rajiv Kumar Osman Ahmed Osama Eisa Alfarazdeg Saad Sara Silva Pereira Marleen Boelaert Pascal Mertens Michael A Miles IgG1 as a potential biomarker of post-chemotherapeutic relapse in visceral leishmaniasis, and adaptation to a rapid diagnostic test. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
BACKGROUND: Visceral leishmaniasis (VL), caused by protozoa of the Leishmania donovani complex, is a widespread parasitic disease of great public health importance; without effective chemotherapy symptomatic VL is usually fatal. Distinction of asymptomatic carriage from progressive disease and the prediction of relapse following treatment are hampered by the lack of prognostic biomarkers for use at point of care. METHODOLOGY/PRINCIPAL FINDINGS: All IgG subclass and IgG isotype antibody levels were determined using unpaired serum samples from Indian and Sudanese patients with differing clinical status of VL, which included pre-treatment active VL, post-treatment cured, post-treatment relapsed, and post kala-azar dermal leishmaniasis (PKDL), as well as seropositive (DAT and/or rK39) endemic healthy controls (EHCs) and seronegative EHCs. L. donovani antigen-specific IgG1 levels were significantly elevated in relapsed versus cured VL patients (p<0.0001). Using paired Indian VL sera, consistent with the known IgG1 half-life, IgG1 levels had not decreased significantly at day 30 after the start of treatment (p = 0.8304), but were dramatically decreased by 6 months compared to day 0 (p = 0.0032) or day 15 (p<0.0001) after start of treatment. Similarly, Sudanese sera taken soon after treatment did not show a significant change in the IgG1 levels (p = 0.3939). Two prototype lateral flow immunochromatographic rapid diagnostic tests (RDTs) were developed to detect IgG1 levels following VL treatment: more than 80% of the relapsed VL patients were IgG1 positive; at least 80% of the cured VL patients were IgG1 negative (p<0.0001). CONCLUSIONS/SIGNIFICANCE: Six months after treatment of active VL, elevated levels of specific IgG1 were associated with treatment failure and relapse, whereas no IgG1 or low levels were detected in cured VL patients. A lateral flow RDT was successfully developed to detect anti-Leishmania IgG1 as a potential biomarker of post-chemotherapeutic relapse. |
format |
Article in Journal/Newspaper |
author |
Tapan Bhattacharyya Armon Ayandeh Andrew K Falconar Shyam Sundar Sayda El-Safi Marissa A Gripenberg Duncan E Bowes Caroline Thunissen Om Prakash Singh Rajiv Kumar Osman Ahmed Osama Eisa Alfarazdeg Saad Sara Silva Pereira Marleen Boelaert Pascal Mertens Michael A Miles |
author_facet |
Tapan Bhattacharyya Armon Ayandeh Andrew K Falconar Shyam Sundar Sayda El-Safi Marissa A Gripenberg Duncan E Bowes Caroline Thunissen Om Prakash Singh Rajiv Kumar Osman Ahmed Osama Eisa Alfarazdeg Saad Sara Silva Pereira Marleen Boelaert Pascal Mertens Michael A Miles |
author_sort |
Tapan Bhattacharyya |
title |
IgG1 as a potential biomarker of post-chemotherapeutic relapse in visceral leishmaniasis, and adaptation to a rapid diagnostic test. |
title_short |
IgG1 as a potential biomarker of post-chemotherapeutic relapse in visceral leishmaniasis, and adaptation to a rapid diagnostic test. |
title_full |
IgG1 as a potential biomarker of post-chemotherapeutic relapse in visceral leishmaniasis, and adaptation to a rapid diagnostic test. |
title_fullStr |
IgG1 as a potential biomarker of post-chemotherapeutic relapse in visceral leishmaniasis, and adaptation to a rapid diagnostic test. |
title_full_unstemmed |
IgG1 as a potential biomarker of post-chemotherapeutic relapse in visceral leishmaniasis, and adaptation to a rapid diagnostic test. |
title_sort |
igg1 as a potential biomarker of post-chemotherapeutic relapse in visceral leishmaniasis, and adaptation to a rapid diagnostic test. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2014 |
url |
https://doi.org/10.1371/journal.pntd.0003273 https://doaj.org/article/478f2acb1fec4ec7a5db4327c5ceac98 |
long_lat |
ENVELOPE(-63.733,-63.733,-64.983,-64.983) |
geographic |
Arctic Azar Indian |
geographic_facet |
Arctic Azar Indian |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 8, Iss 10, p e3273 (2014) |
op_relation |
http://europepmc.org/articles/PMC4207679?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0003273 https://doaj.org/article/478f2acb1fec4ec7a5db4327c5ceac98 |
op_doi |
https://doi.org/10.1371/journal.pntd.0003273 |
container_title |
PLoS Neglected Tropical Diseases |
container_volume |
8 |
container_issue |
10 |
container_start_page |
e3273 |
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1766345182282776576 |