Improving the coverage and accuracy of syphilis testing: The development of a novel rapid, point-of-care test for confirmatory testing of active syphilis infection and its early evaluation in China and South Africa
Background: Current point-of-care tests (POCT) for syphilis, based on the detection of Treponema pallidum (TP) total antibodies, have limited capacity in distinguishing between active and past/treated syphilis. We report the development and early evaluation of a new prototype POCT based on the detec...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2020-07-01
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| Series: | EClinicalMedicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S258953702030184X |
| _version_ | 1818048704194543616 |
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| author | Minh D. Pham Amy Wise Mary L. Garcia Huy Van Shuning Zheng Yasmin Mohamed Yan Han Wan-Hui Wei Yue-Ping Yin Xiang-Sheng Chen Wayne Dimech Susie Braniff Karl-Günter Technau Stanley Luchters David A. Anderson |
| author_facet | Minh D. Pham Amy Wise Mary L. Garcia Huy Van Shuning Zheng Yasmin Mohamed Yan Han Wan-Hui Wei Yue-Ping Yin Xiang-Sheng Chen Wayne Dimech Susie Braniff Karl-Günter Technau Stanley Luchters David A. Anderson |
| author_sort | Minh D. Pham |
| collection | DOAJ |
| description | Background: Current point-of-care tests (POCT) for syphilis, based on the detection of Treponema pallidum (TP) total antibodies, have limited capacity in distinguishing between active and past/treated syphilis. We report the development and early evaluation of a new prototype POCT based on the detection of TP-IgA antibodies, a novel biomarker for active syphilis. Methods: The TP-IgA POCT (index test) was developed in response to the World Health Organisation (WHO) target product profile (TPP) for a POCT for confirmatory syphilis testing. Two sub-studies were conducted consecutively using 458 pre-characterised stored plasma samples in China (sub-study one, addressing the criteria for the WHO TPP), and 503 venous blood samples collected from pregnant/postpartum women in South Africa (sub-study two, addressing potential clinical utility). Performance of the index test was assessed against standard laboratory-based serology using a combination of treponemal (TPHA) and non-treponemal (rapid plasma reagin [RPR]) tests. Findings: In sub-study one, the index test demonstrated 96·1% (95%CI=91·7%-98·5%) sensitivity and 84·7% (95%CI=80·15–88·6%) specificity for identification of active syphilis (TPHA positive, RPR positive). It correctly identified 71% (107/150) samples of past-treated syphilis (TPHA positive, RPR negative). In sub-study two, the index test achieved 100% (95%CI=59%-100%) sensitivity for active syphilis and correctly identified all nine women with past syphilis. Interpretation: The TP-IgA POCT has met the WHO TPP for a POCT for diagnosis of active syphilis and demonstrated its potential utility in a clinical setting. Future studies are warranted to evaluate field performance of the final manufactured test. Funding: Saving Lives at Birth: Grand Challenge for Development, Thrasher Research Fund, and the Victorian Government Operational Infrastructure Scheme. |
| first_indexed | 2024-12-10T10:25:55Z |
| format | Article |
| id | doaj.art-9f5788828cab4542a8e43803a786d962 |
| institution | Directory Open Access Journal |
| issn | 2589-5370 |
| language | English |
| last_indexed | 2024-12-10T10:25:55Z |
| publishDate | 2020-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EClinicalMedicine |
| spelling | doaj.art-9f5788828cab4542a8e43803a786d9622022-12-22T01:52:43ZengElsevierEClinicalMedicine2589-53702020-07-0124100440Improving the coverage and accuracy of syphilis testing: The development of a novel rapid, point-of-care test for confirmatory testing of active syphilis infection and its early evaluation in China and South AfricaMinh D. Pham0Amy Wise1Mary L. Garcia2Huy Van3Shuning Zheng4Yasmin Mohamed5Yan Han6Wan-Hui Wei7Yue-Ping Yin8Xiang-Sheng Chen9Wayne Dimech10Susie Braniff11Karl-Günter Technau12Stanley Luchters13David A. Anderson14Burnet Institute, 85 Commercial Road, Melbourne, Victoria 3004, Australia; School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia; Corresponding author at: Burnet Institute, 85 Commercial Road, Melbourne, Victoria 3004, Australia.Empilweni Services and Research Unit, Department of Paediatrics & Child Health, Rahima Moosa Mother and Child Hospital, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, South AfricaBurnet Institute, 85 Commercial Road, Melbourne, Victoria 3004, AustraliaBurnet Institute, 85 Commercial Road, Melbourne, Victoria 3004, AustraliaBurnet Institute, 85 Commercial Road, Melbourne, Victoria 3004, AustraliaBurnet Institute, 85 Commercial Road, Melbourne, Victoria 3004, Australia; School of Public Health and Preventive Medicine, Monash University, Melbourne, AustraliaNational Center for STD Control, China Center for Disease Control and Prevention, Nanjing, PR China; Chinese Academy of Medical Sciences Institute of Dermatology and Hospital of Skin Diseases, Nanjing, PR ChinaNational Center for STD Control, China Center for Disease Control and Prevention, Nanjing, PR China; Chinese Academy of Medical Sciences Institute of Dermatology and Hospital of Skin Diseases, Nanjing, PR ChinaNational Center for STD Control, China Center for Disease Control and Prevention, Nanjing, PR China; Chinese Academy of Medical Sciences Institute of Dermatology and Hospital of Skin Diseases, Nanjing, PR ChinaNational Center for STD Control, China Center for Disease Control and Prevention, Nanjing, PR China; Chinese Academy of Medical Sciences Institute of Dermatology and Hospital of Skin Diseases, Nanjing, PR ChinaNational Serology Reference Laboratory, Melbourne, AustraliaNational Serology Reference Laboratory, Melbourne, AustraliaEmpilweni Services and Research Unit, Department of Paediatrics & Child Health, Rahima Moosa Mother and Child Hospital, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, South AfricaBurnet Institute, 85 Commercial Road, Melbourne, Victoria 3004, Australia; School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia; Department of Population Health, Aga Khan University, Nairobi, KenyaBurnet Institute, 85 Commercial Road, Melbourne, Victoria 3004, Australia; Nanjing BioPoint Diagnostic Technology, Nanjing, PR ChinaBackground: Current point-of-care tests (POCT) for syphilis, based on the detection of Treponema pallidum (TP) total antibodies, have limited capacity in distinguishing between active and past/treated syphilis. We report the development and early evaluation of a new prototype POCT based on the detection of TP-IgA antibodies, a novel biomarker for active syphilis. Methods: The TP-IgA POCT (index test) was developed in response to the World Health Organisation (WHO) target product profile (TPP) for a POCT for confirmatory syphilis testing. Two sub-studies were conducted consecutively using 458 pre-characterised stored plasma samples in China (sub-study one, addressing the criteria for the WHO TPP), and 503 venous blood samples collected from pregnant/postpartum women in South Africa (sub-study two, addressing potential clinical utility). Performance of the index test was assessed against standard laboratory-based serology using a combination of treponemal (TPHA) and non-treponemal (rapid plasma reagin [RPR]) tests. Findings: In sub-study one, the index test demonstrated 96·1% (95%CI=91·7%-98·5%) sensitivity and 84·7% (95%CI=80·15–88·6%) specificity for identification of active syphilis (TPHA positive, RPR positive). It correctly identified 71% (107/150) samples of past-treated syphilis (TPHA positive, RPR negative). In sub-study two, the index test achieved 100% (95%CI=59%-100%) sensitivity for active syphilis and correctly identified all nine women with past syphilis. Interpretation: The TP-IgA POCT has met the WHO TPP for a POCT for diagnosis of active syphilis and demonstrated its potential utility in a clinical setting. Future studies are warranted to evaluate field performance of the final manufactured test. Funding: Saving Lives at Birth: Grand Challenge for Development, Thrasher Research Fund, and the Victorian Government Operational Infrastructure Scheme.http://www.sciencedirect.com/science/article/pii/S258953702030184XSyphilisIgADiagnostic accuracyPoint of care testSouth AfricaChina |
| spellingShingle | Minh D. Pham Amy Wise Mary L. Garcia Huy Van Shuning Zheng Yasmin Mohamed Yan Han Wan-Hui Wei Yue-Ping Yin Xiang-Sheng Chen Wayne Dimech Susie Braniff Karl-Günter Technau Stanley Luchters David A. Anderson Improving the coverage and accuracy of syphilis testing: The development of a novel rapid, point-of-care test for confirmatory testing of active syphilis infection and its early evaluation in China and South Africa EClinicalMedicine Syphilis IgA Diagnostic accuracy Point of care test South Africa China |
| title | Improving the coverage and accuracy of syphilis testing: The development of a novel rapid, point-of-care test for confirmatory testing of active syphilis infection and its early evaluation in China and South Africa |
| title_full | Improving the coverage and accuracy of syphilis testing: The development of a novel rapid, point-of-care test for confirmatory testing of active syphilis infection and its early evaluation in China and South Africa |
| title_fullStr | Improving the coverage and accuracy of syphilis testing: The development of a novel rapid, point-of-care test for confirmatory testing of active syphilis infection and its early evaluation in China and South Africa |
| title_full_unstemmed | Improving the coverage and accuracy of syphilis testing: The development of a novel rapid, point-of-care test for confirmatory testing of active syphilis infection and its early evaluation in China and South Africa |
| title_short | Improving the coverage and accuracy of syphilis testing: The development of a novel rapid, point-of-care test for confirmatory testing of active syphilis infection and its early evaluation in China and South Africa |
| title_sort | improving the coverage and accuracy of syphilis testing the development of a novel rapid point of care test for confirmatory testing of active syphilis infection and its early evaluation in china and south africa |
| topic | Syphilis IgA Diagnostic accuracy Point of care test South Africa China |
| url | http://www.sciencedirect.com/science/article/pii/S258953702030184X |
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