Diagnosis of Human Leptospirosis: Comparison of Microscopic Agglutination Test with Recombinant LigA/B Antigen-Based In-House IgM Dot ELISA Dipstick Test and Latex Agglutination Test Using Bayesian Latent Class Model and MAT as Gold Standard
Sujit Kumar Behera,
Thankappan Sabarinath,
Balasubramanian Ganesh,
Prasanta Kumar K. Mishra,
Roshan Niloofa,
Kuppusamy Senthilkumar,
Med Ram Verma,
Abhishek Hota,
Shanmugam Chandrasekar,
Yosef Deneke,
Ashok Kumar,
Muruganandam Nagarajan,
Deepanker Das,
Sasmita Khatua,
Radhakrishna Sahu,
Syed Atif Ali
Affiliations
Sujit Kumar Behera
Department of Epidemiology & Public Health, Central University of Tamil Nadu, Thiruvarur 610005, India
Thankappan Sabarinath
Indian Veterinary Research Institute, Bareilly 243122, India
Balasubramanian Ganesh
Indian Council of Medical Research-National Institute of Epidemiology, Chennai 600077, India
Prasanta Kumar K. Mishra
Faculty of Veterinary and Animal Sciences, Rajiv Gandhi South Campus (RGSC), Banaras Hindu University (BHU), Mirzapur 231001, India
Roshan Niloofa
Institute of Biochemistry, Molecular Biology and Biotechnology, University of Colombo, Colombo 00700, Sri Lanka
Kuppusamy Senthilkumar
Zoonosis Research Lab, Tamil Nadu Veterinary and Animal Sciences University, Chennai 600051, India
Med Ram Verma
Livestock Economics and Statistics Division, ICAR-Indian Veterinary Research Institute (ICAR-IVRI), Bareilly 243122, India
Abhishek Hota
Department of Animal Science, Centurion University of Technology and Management, Paralakhemundi 761211, India
Shanmugam Chandrasekar
Biochemistry Laboratory, ICAR-Indian Veterinary Research Institute (ICAR-IVRI), Mukteswar 263138, India
Yosef Deneke
School of Veterinary Medicine, Jimma University, Jimma 378, Ethiopia
Ashok Kumar
Assistant Director General (ICAR), Krishi Bhawan, New Delhi 110001, India
Muruganandam Nagarajan
Indian Council of Medical Research-Regional Medical Research Centre, Port Blair 744103, India
Deepanker Das
National Institute of Research in Environmental Health, Bhopal 462030, India
Sasmita Khatua
Department of Microbiology, SCB Medical College, Cuttack 753007, India
Radhakrishna Sahu
AVAS, Saraskana, Mayurbhanj 757051, India
Syed Atif Ali
Institute of Chemistry, Academia Sinica, Taipei 115024, Taiwan
Leptospirosis is a spirochaetal infection that possesses a broad host range affecting almost all mammals. In the present study, the microscopic agglutination test (MAT) was compared with recombinant LigA/B antigen-based point-of-care diagnostics such as the in-house IgM dot ELISA dipstick test (IgM- DEDT) and the latex agglutination test (LAT) for the serodiagnosis of human leptospirosis. The comparison of the MAT with these two point–of-care diagnostics was performed using the MAT as the gold standard test and using Bayesian latent class modelling (BLCM), which considers all diagnostic tests as imperfect. The N-terminal conserved region of the LigA/B protein spanning the first to fifth big tandem repeat domains (rLigA/BCon1-5) was employed as a serodiagnostic marker in both of the bedside assays. A total of 340 serum samples collected from humans involved in high risk occupations were screened using the MAT, IgM DEDT and LAT. During the early phase of leptospirosis, BLCM analysis showed that the IgM DEDT and LAT had similar sensitivities (99.6 (96.0–100)) and (99.5 (95.2–100)), respectively, while the single acute phase MAT had the lowest sensitivity (83.3 (72.8–91.3)). Both the IgM DEDT and the LAT may be superior to the single acute phase MAT in terms of sensitivity during the early phase of infection and may be suitable for the early diagnosis of leptospirosis. However, BLCM analysis revealed that the use of both acute and convalescent samples substantially increased the sensitivity of the final MAT (98.2% (93.0–99.8%)) as a test to diagnose human leptospirosis. Both the IgM DEDT and LAT can be employed as bedside spot tests in remote locations where the MAT is not easily accessible.
