Accuracy of four rapid diagnostic tests (RDTs) for human leptospirosis diagnosis in Indonesia

ABSTRACT Leptospirosis is an endemic zoonotic disease with protean clinical manifestations caused by pathogenic spirochetes of the Leptospira genus. The microscopic agglutination test (MAT) is the gold standard for leptospirosis diagnosis and can only be conducted in a reference laboratory. Therefor...

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Main Authors: Farida Handayani, Endah Tri Widanarti, Citra W. Kusuma, Ristiyanto Ristiyanto, Amin Soebandrio, Muhammad Hussein Gasem
Format: Article
Language:English
Published: American Society for Microbiology 2025-06-01
Series:Microbiology Spectrum
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Online Access:https://journals.asm.org/doi/10.1128/spectrum.01524-24
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author Farida Handayani
Endah Tri Widanarti
Citra W. Kusuma
Ristiyanto Ristiyanto
Amin Soebandrio
Muhammad Hussein Gasem
author_facet Farida Handayani
Endah Tri Widanarti
Citra W. Kusuma
Ristiyanto Ristiyanto
Amin Soebandrio
Muhammad Hussein Gasem
author_sort Farida Handayani
collection DOAJ
description ABSTRACT Leptospirosis is an endemic zoonotic disease with protean clinical manifestations caused by pathogenic spirochetes of the Leptospira genus. The microscopic agglutination test (MAT) is the gold standard for leptospirosis diagnosis and can only be conducted in a reference laboratory. Therefore, alternative tests, such as the IgM anti-Leptospira rapid diagnostic test (RDT), are preferred for general use. In this study, we aimed to compare the accuracy of four products of anti-Leptospira IgM detection RDTs, which are available in Indonesia, against the gold standard of Leptospira MAT. This study was a diagnostic validation test using bioarchived serum from 364 human serum samples tested by MAT from August to September 2020 in Demak, Central Java, Indonesia. The four products were (i) Fokus Leptospira, (ii) Answer Leptospira, (iii) SD Bioline Leptospira IgG/IgM, and (iv) Uji Leptospira IgM, sequentially renamed RDT-1 to RDT-4. Interobserver agreements were analyzed using the kappa value. The diagnostic performance of the four RDTs were compared against MAT results as the gold standard. We also evaluated the combination of two RDTs’ performance, which were RDT (1 + 2), RDT (1 + 3), RDT (1 + 4), RDT (2 + 4), and RDT (3 + 4). We found that the kappa coefficients of RDT-1, RDT-2, and RDT-4 were greater than 80%, while RDT-3 had a moderate kappa value of 69.1%. RDT-1, RDT-2, and RDT-4 had moderate to good sensitivities of 78.2%, 74.3%, and 83.6%, respectively, while RDT-3 had the lowest sensitivity at 30.9%. RDT-3 demonstrated the highest specificity. RDT-2 showed the highest predictive value at 75.9%, while RDT-4 showed the highest negative predictive value at 96.9%. In addition, the combination of two RTDs provided better diagnostic performances. The four RDTs performed varied in their ability to diagnose leptospirosis, but only RDT-4 showed a sensitivity of more than 80%. We recommend caution in diagnosing only one RDT result. Testing by other RDTs and confirmation by MAT are strongly recommended.IMPORTANCEThe performance of the anti-Leptospira IgM antibody rapid diagnostic tests (RDTs) has yet to be evaluated. In this study, we compare the accuracy of these four RDTs available in Indonesia against the gold standard of Leptospira microscopic agglutination test (MAT). Utilizing the best performance of RDT in the point of care with limited facilities will be effective since MAT is complicated, laborious, and time-consuming if done at public health centers. The MAT requires maintaining the culture of each live Leptospira strain circulating in the region and needs trained personnel.
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spelling doaj-art-00628fb1a8d8484dbb20eda3865e0caa2025-08-20T02:05:28ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972025-06-0113610.1128/spectrum.01524-24Accuracy of four rapid diagnostic tests (RDTs) for human leptospirosis diagnosis in IndonesiaFarida Handayani0Endah Tri Widanarti1Citra W. Kusuma2Ristiyanto Ristiyanto3Amin Soebandrio4Muhammad Hussein Gasem5Doctoral Program in Biomedical Sciences, Faculty of Medicine, University of Indonesia, Jakarta, IndonesiaResearch Center for Care and Control of Infectious Disease (RC3ID) Universitas Padjadjaran, Bandung, IndonesiaMinistry of the Health Republic of Indonesia, NIHRD IVRCRD, Salatiga, IndonesiaResearch Center for Public Health and Nutrition, National Research and Innovation Agency (BRIN), Jakarta, IndonesiaDepartment of Clinical Microbiology, Faculty of Medicine, University of Indonesia-Dr. Cipto Mangunkusumo Hospital, Jakarta, IndonesiaDivision of Infectious Diseases and Tropical Medicine, Dr. Kariadi Hospital, Semarang, IndonesiaABSTRACT Leptospirosis is an endemic zoonotic disease with protean clinical manifestations caused by pathogenic spirochetes of the Leptospira genus. The microscopic agglutination test (MAT) is the gold standard for leptospirosis diagnosis and can only be conducted in a reference laboratory. Therefore, alternative tests, such as the IgM anti-Leptospira rapid diagnostic test (RDT), are preferred for general use. In this study, we aimed to compare the accuracy of four products of anti-Leptospira IgM detection RDTs, which are available in Indonesia, against the gold standard of Leptospira MAT. This study was a diagnostic validation test using bioarchived serum from 364 human serum samples tested by MAT from August to September 2020 in Demak, Central Java, Indonesia. The four products were (i) Fokus Leptospira, (ii) Answer Leptospira, (iii) SD Bioline Leptospira IgG/IgM, and (iv) Uji Leptospira IgM, sequentially renamed RDT-1 to RDT-4. Interobserver agreements were analyzed using the kappa value. The diagnostic performance of the four RDTs were compared against MAT results as the gold standard. We also evaluated the combination of two RDTs’ performance, which were RDT (1 + 2), RDT (1 + 3), RDT (1 + 4), RDT (2 + 4), and RDT (3 + 4). We found that the kappa coefficients of RDT-1, RDT-2, and RDT-4 were greater than 80%, while RDT-3 had a moderate kappa value of 69.1%. RDT-1, RDT-2, and RDT-4 had moderate to good sensitivities of 78.2%, 74.3%, and 83.6%, respectively, while RDT-3 had the lowest sensitivity at 30.9%. RDT-3 demonstrated the highest specificity. RDT-2 showed the highest predictive value at 75.9%, while RDT-4 showed the highest negative predictive value at 96.9%. In addition, the combination of two RTDs provided better diagnostic performances. The four RDTs performed varied in their ability to diagnose leptospirosis, but only RDT-4 showed a sensitivity of more than 80%. We recommend caution in diagnosing only one RDT result. Testing by other RDTs and confirmation by MAT are strongly recommended.IMPORTANCEThe performance of the anti-Leptospira IgM antibody rapid diagnostic tests (RDTs) has yet to be evaluated. In this study, we compare the accuracy of these four RDTs available in Indonesia against the gold standard of Leptospira microscopic agglutination test (MAT). Utilizing the best performance of RDT in the point of care with limited facilities will be effective since MAT is complicated, laborious, and time-consuming if done at public health centers. The MAT requires maintaining the culture of each live Leptospira strain circulating in the region and needs trained personnel.https://journals.asm.org/doi/10.1128/spectrum.01524-24leptospirosisrapid diagnostic testdiagnostic accuracyIndonesia
spellingShingle Farida Handayani
Endah Tri Widanarti
Citra W. Kusuma
Ristiyanto Ristiyanto
Amin Soebandrio
Muhammad Hussein Gasem
Accuracy of four rapid diagnostic tests (RDTs) for human leptospirosis diagnosis in Indonesia
Microbiology Spectrum
leptospirosis
rapid diagnostic test
diagnostic accuracy
Indonesia
title Accuracy of four rapid diagnostic tests (RDTs) for human leptospirosis diagnosis in Indonesia
title_full Accuracy of four rapid diagnostic tests (RDTs) for human leptospirosis diagnosis in Indonesia
title_fullStr Accuracy of four rapid diagnostic tests (RDTs) for human leptospirosis diagnosis in Indonesia
title_full_unstemmed Accuracy of four rapid diagnostic tests (RDTs) for human leptospirosis diagnosis in Indonesia
title_short Accuracy of four rapid diagnostic tests (RDTs) for human leptospirosis diagnosis in Indonesia
title_sort accuracy of four rapid diagnostic tests rdts for human leptospirosis diagnosis in indonesia
topic leptospirosis
rapid diagnostic test
diagnostic accuracy
Indonesia
url https://journals.asm.org/doi/10.1128/spectrum.01524-24
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