Molecular and serological diagnostic of leptospirosis: a review (2014–2020)
DOI:
https://doi.org/10.33448/rsd-v11i2.25471Keywords:
Serological tests; Immunochemical tests; Molecular diagnosis; Leptospirosis; Recombinant proteins.Abstract
Leptospirosis is a zoonosis caused by pathogenic bacteria of the genus Leptospira. This disease affects several animals and humans. Symptoms of leptospirosis can range from mild to severe, may in some cases lead to death. For the diagnosis of leptospirosis, the microscopic agglutination test is considered the “gold standard”; however, it has limitations and studies are being conducted to develop alternative methods of screening and diagnosis of leptospirosis. Serological and immunochemical tests using Leptospira recombinant antigens in combination to molecular tests may be an alternative. In this study, we reported the advances achieved from 2014 until 2020 in controlling leptospirosis based on serological tests using recombinant antigens and molecular diagnosis.
References
Adler, B., & de la Pena Moctezuma, A. (2010). Leptospira and leptospirosis. Vet Microbiol, 140(3-4), 287-296. doi: 10.1016/j.vetmic.2009.03.012
Ahmed, A., van der Linden, H., & Hartskeerl, R. A. (2014). Development of a recombinase polymerase amplification assay for the detection of pathogenic Leptospira. Int J Environ Res Public Health, 11(5), 4953-4964. doi: 10.3390/ijerph110504953
Alizadeh, S. A., Abdolahpour, G., Pourmand, M. R., Naserpour, T., Najafipour, R., & Eshraghi, S. S. (2014). Evaluation of New ELISA based on rLsa63 - rLipL32 antigens for serodiagnosis of Human Leptospirosis. Iran J Microbiol, 6(3), 184-189.
Anita, K., Premlatha, M. M., Kanagavel, M., Akino Mercy, C. S., Raja, V., Shanmughapriya, S., & Natarajaseenivasan, K. (2016). Evaluation of combined B cell specific N-terminal immunogenic domains of LipL21 for diagnosis of leptospirosis. Int J Biol Macromol, 91, 465-470. doi: 10.1016/j.ijbiomac.2016.05.109
Bharti, A. R., Nally, J. E., Ricaldi, J. N., Matthias, M. A., Diaz, M. M., Lovett, M. A., . . . Peru-United States Leptospirosis, C. (2003). Leptospirosis: a zoonotic disease of global importance. Lancet Infect Dis, 3(12), 757-771.
Brownlow, T., Kavanagh, O. V., Logan, E. F., Hartskeerl, R. A., Savage, R., Palmer, M. F., . . . Ellis, W. A. (2014). 'Leptorapide' - a one-step assay for rapid diagnosis of human leptospirosis. Epidemiol Infect, 142(6), 1182-1187. doi: 10.1017/S0950268813002112
Caimi, K., Repetto, S. A., Varni, V., & Ruybal, P. (2017). Leptospira species molecular epidemiology in the genomic era. Infect Genet Evol, 54, 478-485. doi: 10.1016/j.meegid.2017.08.013
Chang, M. Y., Cheng, Y. C., Hsu, S. H., Ma, T. L., Chou, L. F., Hsu, H. H., Tian, Y. C., Chen, Y. C., Sun, Y. J., Hung, C. C., Pan, R. L., & Yang, C. W. (2016). Leptospiral outer membrane protein LipL32 induces inflammation and kidney injury in zebrafish larvae. Scientific reports, 6, 27838. https://doi.org/10.1038/srep27838
Conrad, N. L., Cruz McBride, F. W., Souza, J. D., Silveira, M. M., Felix, S., Mendonca, K. S., . . . McBride, A. J. (2017). LigB subunit vaccine confers sterile immunity against challenge in the hamster model of leptospirosis. PLoS Negl Trop Dis, 11(3), e0005441. doi: 10.1371/journal.pntd.0005441
Courdurie, C., Le Govic, Y., Bourhy, P., Alexer, D., Pailla, K., Theodose, R., . . . Olive, C. (2017). Evaluation of different serological assays for early diagnosis of leptospirosis in Martinique (French West Indies). PLoS Negl Trop Dis, 11(6), e0005678. doi: 10.1371/journal.pntd.0005678
da Cunha, C. E. P., Bettin, E. B., Bakry, A., Seixas Neto, A. C. P., Amaral, M. G., & Dellagostin, O. A. (2019). Evaluation of different strategies to promote a protective immune response against leptospirosis using a recombinant LigA and LigB chimera. Vaccine, 37(13), 1844-1852. doi: 10.1016/j.vaccine.2019.02.010
Deneke, Y., Sabarinath, T., Gogia, N., Lalsiamthara, J., Viswas, K. N., & Chaudhuri, P. (2014). Evaluation of recombinant LigB antigen-based indirect ELISA and latex agglutination test for the serodiagnosis of bovine leptospirosis in India. Mol Cell Probes, 28(4), 141-146. doi: 10.1016/j.mcp.2014.01.001
Denipitiya, D. T., Chandrasekharan, N. V., Abeyewickreme, W., Hartskeerl, C. M., Hartskeerl, R. A., Jiffrey, A. M., & Hapugoda, M. D. (2016). Application of a real time Polymerase Chain Reaction (PCR) assay for the early diagnosis of human leptospirosis in Sri Lanka. Biologicals, 44(6), 497-502. doi: 10.1016/j.biologicals.2016.09.004
Esteves, L. M., Bulhoes, S. M., Branco, C. C., Carreira, T., Vieira, M. L., Gomes-Solecki, M., & Mota-Vieira, L. (2018). Diagnosis of Human Leptospirosis in a Clinical Setting: Real-Time PCR High Resolution Melting Analysis for Detection of Leptospira at the Onset of Disease. Sci Rep, 8(1), 9213. doi: 10.1038/s41598-018-27555-2
Ghazali-Bina, M., Pourmand, M. R., Mirshafiey, A., Bakhtiari, R., Khaledi, A., Kazemian, H., . . . Eshraghi, S. (2019). Vaccine potential of LenA and LcpA proteins of Leptospira interrogans in combination with Escherichia coli heat-labile enterotoxin, B subunit (LTB). Iran J Microbiol, 11(1), 39-47.
Gokmen, T. G., Soyal, A., Kalayci, Y., Onlen, C., & Koksal, F. (2016). Comparison of 16S rRNA-PCR-RFLP, LipL32-PCR and OmpL1-PCR methods in the diagnosis of leptospirosis. Rev Inst Med Trop Sao Paulo, 58, 64. doi: 10.1590/S1678-9946201658064
Gouveia, E. L., Metcalfe, J., de Carvalho, A. L., Aires, T. S., Villasboas-Bisneto, J. C., Queirroz, A., . . . Ko, A. I. (2008). Leptospirosis-associated severe pulmonary hemorrhagic syndrome, Salvador, Brazil. Emerg Infect Dis, 14(3), 505-508. doi: 10.3201/eid1403.071064
Gregoire, F., Bakinahe, R., Petitjean, T., Boarbi, S., Delooz, L., Fretin, D., . . . Mori, M. (2020). Laboratory Diagnosis of Bovine Abortions Caused by Non-Maintenance Pathogenic Leptospira spp.: Necropsy, Serology and Molecular Study Out of a Belgian Experience. Pathogens, 9(6). doi: 10.3390/pathogens9060413
Grippi, F., Giudice, E., Pietro, S. D., Sciacca, C., Santangelo, F., Galluzzo, P., . . . Guercio, A. (2020). Leptospira interrogans Serogroup Sejroe Serovar Hardjo in Aborting Cows: Two Herd Cases in Sicily (Italy). J Vet Res, 64(1), 73-78. doi: 10.2478/jvetres-2020-0021
Guglielmini, J., Bourhy, P., Schiettekatte, O., Zinini, F., Brisse, S., & Picardeau, M. (2019). Genus-wide Leptospira core genome multilocus sequence typing for strain taxonomy and global surveillance. PLoS Negl Trop Dis, 13(4), e0007374. doi: 10.1371/journal.pntd.0007374
Haake, D. A., Chao, G., Zuerner, R. L., Barnett, J. K., Barnett, D., Mazel, M., . . . Bolin, C. A. (2000). The leptospiral major outer membrane protein LipL32 is a lipoprotein expressed during mammalian infection. Infect Immun, 68(4), 2276-2285. doi: 10.1128/iai.68.4.2276-2285.2000
Haake, D. A., & Matsunaga, J. (2002). Characterization of the leptospiral outer membrane and description of three novel leptospiral membrane proteins. Infect Immun, 70(9), 4936-4945. doi: 10.1128/iai.70.9.4936-4945.2002
Jorge, S., Kremer, F. S., Oliveira, N. R., Navarro, G., Guimaraes, A. M., Sanchez, C. D., . . . Dellagostin, O. A. (2018). Whole-genome sequencing of Leptospira interrogans from southern Brazil: genetic features of a highly virulent strain. Mem Inst Oswaldo Cruz, 113(2), 80-86. doi: 10.1590/0074-02760170130
Kitashoji, E., Koizumi, N., Lacuesta, T. L., Usuda, D., Ribo, M. R., Tria, E. S., . . . Ariyoshi, K. (2015). Diagnostic Accuracy of Recombinant Immunoglobulin-like Protein A-Based IgM ELISA for the Early Diagnosis of Leptospirosis in the Philippines. PLoS Negl Trop Dis, 9(6), e0003879. doi: 10.1371/journal.pntd.0003879
Ko, A. I., Goarant, C., & Picardeau, M. (2009). Leptospira: the dawn of the molecular genetics era for an emerging zoonotic pathogen. Nat Rev Microbiol, 7(10), 736-747. doi: 10.1038/nrmicro2208
Lam, J. Y., Low, G. K., & Chee, H. Y. (2020). Diagnostic accuracy of genetic markers and nucleic acid techniques for the detection of Leptospira in clinical samples: A meta-analysis. PLoS Negl Trop Dis, 14(2), e0008074. doi: 10.1371/journal.pntd.0008074
Lessa-Aquino, C., Lindow, J. C., Randall, A., Wunder, E., Pablo, J., Nakajima, R., . . . Felgner, P. L. (2017). Distinct antibody responses of patients with mild and severe leptospirosis determined by whole proteome microarray analysis. PLoS Negl Trop Dis, 11(1), e0005349. doi: 10.1371/journal.pntd.0005349
Levett, P. N. (2001). Leptospirosis. Clin Microbiol Rev, 14(2), 296-326. doi: 10.1128/CMR.14.2.296-326.2001
Lo, M., Cordwell, S. J., Bulach, D. M., & Adler, B. (2009). Comparative transcriptional and translational analysis of leptospiral outer membrane protein expression in response to temperature. PLoS Negl Trop Dis, 3(12), e560. doi: 10.1371/journal.pntd.0000560
McBride, A. J., Athanazio, D. A., Reis, M. G., & Ko, A. I. (2005). Leptospirosis. Curr Opin Infect Dis, 18(5), 376-386.
Mohd Ali, M. R., Lih Huey, L., Foo, P. C., Goay, Y. X., Ismail, A. S., Mustaffa, K. M. F., . . . Yean Yean, C. (2019). Duplex TaqMan Hydrolysis Probe-Based Molecular Assay for Simultaneous Detection and Differentiation of Burkholderia pseudomallei and Leptospira spp. DNA. Biomed Res Int, 2019, 9451791. doi: 10.1155/2019/9451791
Mohd Ali, M. R., Mohamad Safiee, A. W., Yusof, N. Y., Fauzi, M. H., Yean Yean, C., & Ismail, N. (2017). Isolation of Leptospira kmetyi from residential areas of patients with leptospirosis in Kelantan, Malaysia. J Infect Public Health. doi: 10.1016/j.jiph.2017.12.008
Mohd Ali, M. R., Mohd Safee, A. W., Ismail, N. H., Abu Sapian, R., Mat Hussin, H., Ismail, N., & Yean Yean, C. (2018). Development and validation of pan-Leptospira Taqman qPCR for the detection of Leptospira spp. in clinical specimens. Mol Cell Probes, 38, 1-6. doi: 10.1016/j.mcp.2018.03.001
Monica, N. I., Rathinasabapathi, P., & Ramya, M. (2019). Development of real-time loop-mediated isothermal amplification (RealAmp) method for sensitive and rapid detection of pathogenic and nonpathogenic Leptospira. Lett Appl Microbiol, 68(2), 196-203. doi: 10.1111/lam.13108
Mwachui, M. A., Crump, L., Hartskeerl, R., Zinsstag, J., & Hattendorf, J. (2015). Environmental and Behavioural Determinants of Leptospirosis Transmission: A Systematic Review. PLoS Negl Trop Dis, 9(9), e0003843. doi: 10.1371/journal.pntd.0003843
Nagalingam, M., Thirumalesh, S. R., Kalleshamurthy, T., Niharika, N., Balamurugan, V., Shome, R., . . . Rahman, H. (2015). Comparative evaluation of recombinant LigB protein and heat-killed antigen-based latex agglutination test with microscopic agglutination test for diagnosis of bovine leptospirosis. Trop Anim Health Prod, 47(7), 1329-1335. doi: 10.1007/s11250-015-0867-7
Nagraik, R., Kaushal, A., Gupta, S., Dhar, P., Sethi, S., & Kumar, D. (2019). Optimized DNA-based bioassay for Leptospira interrogans detection: a novel platform for leptospirosis diagnosis. 3 Biotech, 9(7), 284. doi: 10.1007/s13205-019-1815-4
Nally, J. E., Whitelegge, J. P., Bassilian, S., Blanco, D. R., & Lovett, M. A. (2007). Characterization of the outer membrane proteome of Leptospira interrogans expressed during acute lethal infection. Infect Immun, 75(2), 766-773. doi: 10.1128/IAI.00741-06
Nhan, T. X., Teissier, A., Roche, C., & Musso, D. (2014). Sensitivity of real-time PCR performed on dried sera spotted on filter paper for diagnosis of leptospirosis. J Clin Microbiol, 52(8), 3075-3077. doi: 10.1128/JCM.00503-14
Oliveira, T. L., Rizzi, C., da Cunha, C. E. P., Dorneles, J., Seixas Neto, A. C. P., Amaral, M. G., . . . Dellagostin, O. A. (2019). Recombinant BCG strains expressing chimeric proteins derived from Leptospira protect hamsters against leptospirosis. Vaccine, 37(6), 776-782. doi: 10.1016/j.vaccine.2018.12.050
Oliveira, T. L., Schuch, R. A., Inda, G. R., Roloff, B. C., Neto, A., Amaral, M., . . . Hartwig, D. D. (2018). LemA and Erp Y-like recombinant proteins from Leptospira interrogans protect hamsters from challenge using AddaVax as adjuvant. Vaccine, 36(19), 2574-2580. doi: 10.1016/j.vaccine.2018.03.078
Padilha, B. C. R., Simao, H. Q., Oliveira, T. L., & Hartwig, D. D. (2019). The use of ErpY-like recombinant protein from Leptospira interrogans in the development of an immunodiagnostic test for swine leptospirosis. Acta Trop, 193, 31-34. doi: 10.1016/j.actatropica.2019.01.027
Perez, L. J., Lanka, S., DeShambo, V. J., Fredrickson, R. L., & Maddox, C. W. (2020). A Validated Multiplex Real-Time PCR Assay for the Diagnosis of Infectious Leptospira spp.: A Novel Assay for the Detection and Differentiation of Strains From Both Pathogenic Groups I and II. Front Microbiol, 11, 457. doi: 10.3389/fmicb.2020.00457
Petrakovsky, J., Bianchi, A., Fisun, H., Najera-Aguilar, P., & Pereira, M. M. (2014). Animal leptospirosis in Latin America and the Caribbean countries: reported outbreaks and literature review (2002-2014). Int J Environ Res Public Health, 11(10), 10770-10789. doi: 10.3390/ijerph111010770
Philip, N., Bahtiar Affendy, N., Ramli, S. N. A., Arif, M., Raja, P., Nagandran, E., . . . Neela, V. K. (2020). Leptospira interrogans and Leptospira kirschneri are the dominant Leptospira species causing human leptospirosis in Central Malaysia. PLoS Negl Trop Dis, 14(3), e0008197. doi: 10.1371/journal.pntd.0008197
Picardeau, M. (2017). Virulence of the zoonotic agent of leptospirosis: still terra incognita? Nat Rev Microbiol, 15(5), 297-307. doi: 10.1038/nrmicro.2017.5
Podgorsek, D., Ruzic-Sabljic, E., Logar, M., Pavlovic, A., Remec, T., Baklan, Z., . . . Cerar, T. (2020). Evaluation of real-time PCR targeting the lipL32 gene for diagnosis of Leptospira infection. BMC Microbiol, 20(1), 59. doi: 10.1186/s12866-020-01744-4
Raja, V., Prasad, M., Bothammal, P., Saranya, P., Sumaiya, K., Akino Mercy, C. S., & Natarajaseenivasan, K. (2019). Silver enhanced nano-gold dot blot immunoassay for leptospirosis. J Microbiol Methods, 156, 20-22. doi: 10.1016/j.mimet.2018.11.021
Raja, V., Sobana, S., Mercy, C. S. A., Cotto, B., Bora, D. P., & Natarajaseenivasan, K. (2018). Heterologous DNA prime-protein boost immunization with RecA and FliD offers cross-clade protection against leptospiral infection. Sci Rep, 8(1), 6447. doi: 10.1038/s41598-018-24674-8
Rajapakse, S., Rodrigo, C., Handunnetti, S. M., & Fernando, S. D. (2015). Current immunological and molecular tools for leptospirosis: diagnostics, vaccine design, and biomarkers for predicting severity. Ann Clin Microbiol Antimicrob, 14, 2. doi: 10.1186/s12941-014-0060-2
Rajapakse, S., Weeratunga, P. N., Balaji, K., Ramchandani, K. C., de Silva, U. S., Ranasinghe, S. A., . . . Fernando, S. D. (2020). Seroprevalence of leptospirosis in an endemic mixed urban and semi-urban setting-A community-based study in the district of Colombo, Sri Lanka. PLoS Negl Trop Dis, 14(5), e0008309. doi: 10.1371/journal.pntd.0008309
S. Faine, B. A., C. Bolin, P. Perolat. (1999). Leptospira and Leptospirosis.
Sea-Liang, N., Sereemaspun, A., Patarakul, K., Gaywee, J., Rodkvamtook, W., Srisawat, N., . . . Hemachudha, T. (2019). Development of multiplex PCR for neglected infectious diseases. PLoS Negl Trop Dis, 13(7), e0007440. doi: 10.1371/journal.pntd.0007440
Setubal, J. C., Reis, M., Matsunaga, J., & Haake, D. A. (2006). Lipoprotein computational prediction in spirochaetal genomes. Microbiology, 152(Pt 1), 113-121. doi: 10.1099/mic.0.28317-0
Shiokawa, K., Gamage, C. D., Koizumi, N., Sakoda, Y., Shimizu, K., Tsuda, Y., . . . Arikawa, J. (2016). Evaluation of truncated LipL32 expressed by Escherichia coli and Pichia pastoris for serodiagnosis of Leptospira infection in rodents. J Vet Med Sci, 78(2), 221-230. doi: 10.1292/jvms.15-0325
Sun, A. H., Liu, X. X., & Yan, J. (2020). Leptospirosis is an invasive infectious and systemic inflammatory disease. Biomed J, 43(1), 24-31. doi: 10.1016/j.bj.2019.12.002
Suwancharoen, D., Sittiwicheanwong, B., & Wiratsudakul, A. (2016). Evaluation of loop-mediated isothermal amplification method (LAMP) for pathogenic Leptospira spp. detection with leptospires isolation and real-time PCR. J Vet Med Sci, 78(8), 1299-1302. doi: 10.1292/jvms.15-0702
Thibeaux, R., Iraola, G., Ferres, I., Bierque, E., Girault, D., Soupe-Gilbert, M. E., . . . Goarant, C. (2018). Deciphering the unexplored Leptospira diversity from soils uncovers genomic evolution to virulence. Microb Genom, 4(1). doi: 10.1099/mgen.0.000144
Thongsukkaeng, K., & Boonyom, R. (2018). Development and evaluation of latex agglutination test coating with recombinant antigen, LipL32 for serodiagnosis of human leptospirosis. J Genet Eng Biotechnol, 16(2), 441-446. doi: 10.1016/j.jgeb.2018.10.002
Vanithamani, S., Shanmughapriya, S., Narayanan, R., Raja, V., Kanagavel, M., Sivasankari, K., & Natarajaseenivasan, K. (2015). Lipopolysaccharide Specific Immunochromatography Based Lateral Flow Assay for Serogroup Specific Diagnosis of Leptospirosis in India. PLoS One, 10(9), e0137130. doi: 10.1371/journal.pone.0137130
Victoriano, A. F., Smythe, L. D., Gloriani-Barzaga, N., Cavinta, L. L., Kasai, T., Limpakarnjanarat, K., . . . Adler, B. (2009). Leptospirosis in the Asia Pacific region. BMC Infect Dis, 9, 147. doi: 10.1186/1471-2334-9-147
Vinetz, J. M. (2001). Leptospirosis. Curr Opin Infect Dis, 14(5), 527-538. doi: 10.1097/00001432-200110000-00005
Viratyosin, W., Ingsriswang, S., Pacharawongsakda, E., & Palittapongarnpim, P. (2008). Genome-wide subcellular localization of putative outer membrane and extracellular proteins in Leptospira interrogans serovar Lai genome using bioinformatics approaches. BMC Genomics, 9, 181. doi: 10.1186/1471-2164-9-181
Waggoner, J. J., Balassiano, I., Mohamed-Hadley, A., Vital-Brazil, J. M., Sahoo, M. K., & Pinsky, B. A. (2015). Reverse-Transcriptase PCR Detection of Leptospira: Absence of Agreement with Single-Specimen Microscopic Agglutination Testing. PLoS One, 10(7), e0132988. doi: 10.1371/journal.pone.0132988
Waggoner, J. J., & Pinsky, B. A. (2016). Molecular diagnostics for human leptospirosis. Curr Opin Infect Dis, 29(5), 440-445. doi: 10.1097/QCO.0000000000000295
Wynwood, S. J., Burns, M. A., Graham, G. C., Weier, S. L., McKay, D. B., & Craig, S. B. (2015). Validation of a microsphere immunoassay for serological leptospirosis diagnosis in human serum by comparison to the current gold standard. PLoS Negl Trop Dis, 9(3), e0003636. doi: 10.1371/journal.pntd.0003636
Wynwood, S. J., Burns, M. A., Graham, G. C., Weier, S. L., McKay, D. B., & Craig, S. B. (2016). Serological diagnosis of Leptospirosis in bovine serum samples using a microsphere immunoassay. Vet Rec Open, 3(1), e000148. doi: 10.1136/vetreco-2015-000148
Yang, H. L., Zhu, Y. Z., Qin, J. H., He, P., Jiang, X. C., Zhao, G. P., & Guo, X. K. (2006). In silico and microarray-based genomic approaches to identifying potential vaccine candidates against Leptospira interrogans. BMC Genomics, 7, 293. doi: 10.1186/1471-2164-7-293
Ye, C., Yan, W., Xiang, H., He, H., Yang, M., Ijaz, M., . . . Chang, Y. F. (2014). Recombinant antigens rLipL21, rLoa22, rLipL32 and rLigACon4-8 for serological diagnosis of leptospirosis by enzyme-linked immunosorbent assays in dogs. PLoS One, 9(12), e111367. doi: 10.1371/journal.pone.0111367
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