Design, development and evaluation of rK28-based point-of-care tests for improving rapid diagnosis of visceral leishmaniasis.
BACKGROUND: Visceral leishmaniasis (VL) is diagnosed by microscopic confirmation of the parasite in bone marrow, spleen or lymph node aspirates. These procedures are unsuitable for rapid diagnosis of VL in field settings. The development of rK39-based rapid diagnostic tests (RDT) revolutionized diag...
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ftdoajarticles:oai:doaj.org/article:01b33bf8080e46989b7cabc842a4dedf 2023-05-15T15:17:27+02:00 Design, development and evaluation of rK28-based point-of-care tests for improving rapid diagnosis of visceral leishmaniasis. Sowmya Pattabhi Jacqueline Whittle Raodoh Mohamath Sayda El-Safi Garner G Moulton Jeffrey A Guderian Danny Colombara Asem O Abdoon Maowia M Mukhtar Dinesh Mondal Javan Esfandiari Shailendra Kumar Peter Chun Steven G Reed Ajay Bhatia 2010-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0000822 https://doaj.org/article/01b33bf8080e46989b7cabc842a4dedf EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC2939046?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0000822 https://doaj.org/article/01b33bf8080e46989b7cabc842a4dedf PLoS Neglected Tropical Diseases, Vol 4, Iss 9, p e1000888 (2010) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2010 ftdoajarticles https://doi.org/10.1371/journal.pntd.0000822 2022-12-30T23:12:17Z BACKGROUND: Visceral leishmaniasis (VL) is diagnosed by microscopic confirmation of the parasite in bone marrow, spleen or lymph node aspirates. These procedures are unsuitable for rapid diagnosis of VL in field settings. The development of rK39-based rapid diagnostic tests (RDT) revolutionized diagnosis of VL by offering high sensitivity and specificity in detecting disease in the Indian subcontinent; however, these tests have been less reliable in the African subcontinent (sensitivity range of 75-85%, specificity of 70-92%). We have addressed limitations of the rK39 with a new synthetic polyprotein, rK28, followed by development and evaluation of two new rK28-based RDT prototype platforms. METHODOLOGY/PRINCIPAL FINDINGS: Evaluation of 62 VL-confirmed sera from Sudan provided sensitivities of 96.8% and 93.6% (95% CI = K28: 88.83-99.61%; K39: 84.30-98.21%) and specificities of 96.2% and 92.4% (95% CI = K28: 90.53-98.95%; K39: 85.54-96.65%) for rK28 and rK39, respectively. Of greater interest was the observation that individual VL sera with low rK39 reactivity often had much higher rK28 reactivity. This characteristic of the fusion protein was exploited in the development of rK28 rapid tests, which may prove to be crucial in detecting VL among patients with low rK39 antibody levels. Evaluation of two prototype lateral flow-based rK28 rapid tests on 53 VL patients in Sudan and 73 VL patients in Bangladesh provided promisingly high sensitivities (95.9% [95% CI = 88.46-99.1 in Sudan and 98.1% [95% CI = 89.93-99.95%] in Bangladesh) compared to the rK39 RDT (sensitivities of 86.3% [95% CI = 76.25-93.23%] in Sudan and 88.7% [95% CI = 76.97-95.73%] in Bangladesh). CONCLUSIONS/SIGNIFICANCE: Our study compares the diagnostic accuracy of rK39 and rK28 in detecting active VL cases and our findings indicate that rK28 polyprotein has great potential as a serodiagnostic tool. A new rK28-based RDT will prove to be a valuable asset in simplifying VL disease confirmation at the point-of-care. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Indian PLoS Neglected Tropical Diseases 4 9 e822 |
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 Sowmya Pattabhi Jacqueline Whittle Raodoh Mohamath Sayda El-Safi Garner G Moulton Jeffrey A Guderian Danny Colombara Asem O Abdoon Maowia M Mukhtar Dinesh Mondal Javan Esfandiari Shailendra Kumar Peter Chun Steven G Reed Ajay Bhatia Design, development and evaluation of rK28-based point-of-care tests for improving rapid diagnosis of visceral leishmaniasis. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
BACKGROUND: Visceral leishmaniasis (VL) is diagnosed by microscopic confirmation of the parasite in bone marrow, spleen or lymph node aspirates. These procedures are unsuitable for rapid diagnosis of VL in field settings. The development of rK39-based rapid diagnostic tests (RDT) revolutionized diagnosis of VL by offering high sensitivity and specificity in detecting disease in the Indian subcontinent; however, these tests have been less reliable in the African subcontinent (sensitivity range of 75-85%, specificity of 70-92%). We have addressed limitations of the rK39 with a new synthetic polyprotein, rK28, followed by development and evaluation of two new rK28-based RDT prototype platforms. METHODOLOGY/PRINCIPAL FINDINGS: Evaluation of 62 VL-confirmed sera from Sudan provided sensitivities of 96.8% and 93.6% (95% CI = K28: 88.83-99.61%; K39: 84.30-98.21%) and specificities of 96.2% and 92.4% (95% CI = K28: 90.53-98.95%; K39: 85.54-96.65%) for rK28 and rK39, respectively. Of greater interest was the observation that individual VL sera with low rK39 reactivity often had much higher rK28 reactivity. This characteristic of the fusion protein was exploited in the development of rK28 rapid tests, which may prove to be crucial in detecting VL among patients with low rK39 antibody levels. Evaluation of two prototype lateral flow-based rK28 rapid tests on 53 VL patients in Sudan and 73 VL patients in Bangladesh provided promisingly high sensitivities (95.9% [95% CI = 88.46-99.1 in Sudan and 98.1% [95% CI = 89.93-99.95%] in Bangladesh) compared to the rK39 RDT (sensitivities of 86.3% [95% CI = 76.25-93.23%] in Sudan and 88.7% [95% CI = 76.97-95.73%] in Bangladesh). CONCLUSIONS/SIGNIFICANCE: Our study compares the diagnostic accuracy of rK39 and rK28 in detecting active VL cases and our findings indicate that rK28 polyprotein has great potential as a serodiagnostic tool. A new rK28-based RDT will prove to be a valuable asset in simplifying VL disease confirmation at the point-of-care. |
format |
Article in Journal/Newspaper |
author |
Sowmya Pattabhi Jacqueline Whittle Raodoh Mohamath Sayda El-Safi Garner G Moulton Jeffrey A Guderian Danny Colombara Asem O Abdoon Maowia M Mukhtar Dinesh Mondal Javan Esfandiari Shailendra Kumar Peter Chun Steven G Reed Ajay Bhatia |
author_facet |
Sowmya Pattabhi Jacqueline Whittle Raodoh Mohamath Sayda El-Safi Garner G Moulton Jeffrey A Guderian Danny Colombara Asem O Abdoon Maowia M Mukhtar Dinesh Mondal Javan Esfandiari Shailendra Kumar Peter Chun Steven G Reed Ajay Bhatia |
author_sort |
Sowmya Pattabhi |
title |
Design, development and evaluation of rK28-based point-of-care tests for improving rapid diagnosis of visceral leishmaniasis. |
title_short |
Design, development and evaluation of rK28-based point-of-care tests for improving rapid diagnosis of visceral leishmaniasis. |
title_full |
Design, development and evaluation of rK28-based point-of-care tests for improving rapid diagnosis of visceral leishmaniasis. |
title_fullStr |
Design, development and evaluation of rK28-based point-of-care tests for improving rapid diagnosis of visceral leishmaniasis. |
title_full_unstemmed |
Design, development and evaluation of rK28-based point-of-care tests for improving rapid diagnosis of visceral leishmaniasis. |
title_sort |
design, development and evaluation of rk28-based point-of-care tests for improving rapid diagnosis of visceral leishmaniasis. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2010 |
url |
https://doi.org/10.1371/journal.pntd.0000822 https://doaj.org/article/01b33bf8080e46989b7cabc842a4dedf |
geographic |
Arctic Indian |
geographic_facet |
Arctic Indian |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 4, Iss 9, p e1000888 (2010) |
op_relation |
http://europepmc.org/articles/PMC2939046?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0000822 https://doaj.org/article/01b33bf8080e46989b7cabc842a4dedf |
op_doi |
https://doi.org/10.1371/journal.pntd.0000822 |
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PLoS Neglected Tropical Diseases |
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9 |
container_start_page |
e822 |
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