Evaluation of Combined Rapid Immunoglobulin M and Immunoglobulin G Lateral Flow Assays for the Diagnosis of Leptospirosis, Scrub Typhus, and Hantavirus Infection
DOI:
https://doi.org/10.33192/Smj.2020.34Keywords:
Immunochromatographic assay, leptospirosis, scrub typhus, hantavirusAbstract
Objective: Leptospirosis, scrub typhus, and hantavirus infection are commonly identified as causes of acute undifferentiated fever in rural parts of Asia. Although the characteristic presentations of these infections are well described, many of them present with nonspecific manifestations. Diagnosis is usually made by combined history of exposure, clinical features and positive antibody detection. The development of rapid antibody detection assay, using an immunochromatographic test (ICT) for the diagnosis of multi-diseases, has provided tools for more accurate diagnosis and appropriate antibiotic treatment of the acute undifferentiated fever syndrome.
Methods: We evaluated the diagnostic performance of a commercially available combined rapid ICT for the diagnosis of leptospirosis, scrub typhus, and hantavirus infection, using archived blood samples from 434 patients with laboratory-confirmed leptospirosis (131) or scrub typhus (128), and from patients with other causes of fever as the negative control (175). Polysaccharide of nonpathogenic Leptospira patoc, a chimeric recombinant protein cr56 and two other recombinant proteins, r21 and kr56, from different serotypes of Orientia tsutsugamushi, and 21kDa species-specific antigen and recombinant CNP antigen derived from the Soochong virus were used as antigens for the diagnosis of leptospirosis, scrub typhus, and hantavirus infection in the combined ICT used in this study.
Results: For the diagnosis of leptospirosis; in acute phase, the sensitivity and specificity of the ICT detection of IgM/IgG were 38.2% (95% CI, 29.9- 46.5%), and 99.0% (95% CI 97.9-100%); while in convalescent phase, the same were 84.6% (95%CI, 77.1- 92.0%), and 96.2% (95%CI, 92.5- 99.8%), respectively. For scrub typhus, in acute phase, the sensitivity and specificity of the ICT detection of IgM/IgG were 71.9% (95% CI, 64.1- 79.7%), and 97.4% (95% CI 95.6 - 99.2%); while in convalescent phase, the same were 84.6% (95%CI, 74.8- 94.4%), and 90.2% (95%CI, 85.3- 95.1%) respectively. For hantavirus infection, nine patients had detectable IgM for hantavirus infection. All these cases were diagnosed as scrub typhus by indirect immunofluorescent assay.
Conclusion: The performance of this combined ICT for leptospirosis and scrub typhus were comparable to those published data of other ICTs. However, the rapid test for the diagnosis of leptospirosis, using antigen detection, is needed. Hantavirus infection was not detected in this study population.
References
2. Bhargava A, Ralph R, Chatterjee B. Assessment and initial management of acute undifferentiated fever in tropical and subtropical regions. BMJ. 2018; 363:1-13.
3. Abela-Ridder B, Sikkema R, Hartskeerl RA. Estimating the burden of human leptospirosis. Int J Antimicrob Agents 2010;36(Suppl 1):S5-S7.
4. Watt G, Parola P. Scrub typhus and tropical rickettsioses. Curr Opin Infect Dis 2003;16:429-36.
5. Luce-Fedrow A, Lehman ML, Kelly DJ, Mullins K, Maina AN, StewartR L, et al. A review of scrub typhus (Orientia tsutsugamushi and Related Organisms): Then, Now, and Tomorrow. Trop Med Infect Dis 2018;3(1):8.
6. Suttinont C, Losuwanaluk K, Niwatayakul K, Hoontrakul S, Intaranongpai W, Silpasakorn S, et al. Causes of acute undifferentiated febrile illness in rural Thailand: a prospective observational study. Ann Trop Med Hyg 2006;100:363-70.
7. Kim WK, No JS, Lee SH, Song DH, Lee D, Kim JA, et al. Multiplex PCR-based next-generation sequencing and global diversity of Seoul virus in humans and rats. Emerg Infect Dis 2018;24(2):249-57.
8. Suputthamongkol Y, Nitatpattana N, Chayakulkeeree M, Palabodeewat S, Yoksan S, Gonzalez JP. Hantavirus infection in Thailand: first clinical case report. Southeast Asian J Trop Med Public Health. 2005;36:217-20.
9. Pattamadilok S, Lee B-H, Kumperasart S, Yoshimatsu K, Okumura M, Nakamura I, et al. Geographical distribution of hantaviruses in Thailand and potential human health significance of Thailand virus. Am J Trop Med Hyg 2006;75(5):994-1002.
10. Dahanayaka N, Agampodi S, Bandaranayaka A, Priyankara S, Vinetz J. Hantavirus infection mimicking leptospirosis: how long are we going to rely on clinical suspicion? J Infect Dev Ctries 2014;8:1072-5.
11. Suputtamongkol Y, Niwattayakul K, Suttinont C, Losuwanaluk K, Limpaiboon R, W. Chierakul W, et al. An open, randomized, controlled trial of penicillin, doxycycline, and cefotaxime for patients with severe leptospirosis. Clin Infect Dis 2004;39:1417-24.
12. Thipmontree W, Suputtamongkol Y, Tantibhedhyangkul W, Suttinont C, Wongsawat E, Silpasakorn S. Human leptospirosis trends: northeast Thailand, 2001-2012. Int J Environ Res Public Health 2014;11(8):8542-51.
13. Lee JW, Park S, Kim SH, Christova I, Jacob P, Vanasco NB, et al. J Korean Med Sci 2016;31:183-9.
14. Kim YJ, Yeo SJ, Park, S, Woo Yj, Kim MW, Kim SH, et al. Improvement of the diagnostic sensitivity of scrub typhus using a mixture of recombinant antigens derived from Orientia tsutsugamushi serotypes. J Korean Med Sci 2013;28:672-9.
15. Shin DH, Park S, Kim YJ, Kim S, Kim MS, Woo SD, et al. Development and clinical evaluation of rapid diagnostic kit for hemorrhagic fever with renal syndrome. Glo Adv Res J Med Med Sci 2017;6(12):316-9.
16. Suputtamongkol Y, Pongtavornpinyo W, Lubell Y, Suttinont C, Hoontrakul S, Phimda K, et al. Strategies for diagnosis and treatment of suspected leptospirosis: a cost-benefit analysis. PLoS Nleg Trop Med 2010;4:e610.
17. Maze MJ, Sharples KJ, Allan JK, Rubach MP, Crump JA. Diagnostic accuracy of leptospirosis whole-cell lateral flow assays: a systematic review and meta-analysis. Clin Microbiol Infect 2019;25:437-44.
18. Saraswati K, Day N, Mukaka1 M, Blacksell SD. Scrub typhus point-of-care testing: A systematic review and meta-analysis. PLoS Negl Trop Dis 2018;12(3):e0006330.
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