Detection of human leptospirosis as a cause of acute fever by capture ELISA using a Leptospira interrogans serovar Copenhageni (M20) derived antigen

BMC Infectious Diseases

Ryan C Maves⁵  Eric R Hall⁴  Benjamin Espinosa⁴  Tadeusz J Kochel⁴  Alfredo Guillen⁶  Maruja Bernal²  Rina Meza²  Juan Perez²  Kalina Campos³  Yocelinda Meza²  Eric Halsey²  Matthew Kasper²  Michael Gregory²  Kristen Heitzinger²  Simon Pollett¹  Enrique Canal² 

[1] Sydney Institute of Emerging Infections and Biosecurity, University of Sydney, Sydney, Australia;U.S. Naval Medical Research Unit No. 6, Lima, Peru;Institute of Tropical Medicine ‘Alexander von Humboldt’, Universidad Peruana Cayetano Heredia, Lima, Peru;Naval Medical Research Center, Silver Spring, MD, USA;Division of Infectious Diseases, Naval Medical Center, San Diego, CA, USA;Universidad Nacional Federico Villarreal, Lima, Peru

关键词: Peru;    MAT;    MAC ELISA;    IgM;    Leptospirosis;   

Others  :  1145735
DOI  :  10.1186/1471-2334-13-438

 received in 2013-04-06, accepted in 2013-08-27,  发布年份 2013

【 摘 要 】

Background

Leptospirosis is a potentially lethal zoonosis mainly affecting low-resource tropical countries, including Peru and its neighbouring countries. Timely diagnosis of leptospirosis is critical but may be challenging in the regions where it is most prevalent. The serodiagnostic gold standard microagglutination test (MAT) may be technically prohibitive. Our objective in this study was to assess the sensitivity, specificity, and predictive value of an IgM antibody capture enzyme-linked immunoassay (MAC-ELISA) derived from the M20 strain of Leptospira interrogans serovar Copenhageni (M20) by comparison to MAT, which was used as the gold standard method of diagnosis.

Methods

Acute and convalescent sera from participants participating in a passive febrile surveillance study in multiple regions of Peru were tested by both IgM MAC-ELISA and MAT. The sensitivity, specificity, positive and negative predictive value (PPV, NPV) of the MAC-ELISA assay for acute, convalescent and paired sera by comparison to MAT were calculated.

Results

The sensitivity, specificity, PPV and NPV of the MAC-ELISA assay for acute sera were 92.3%, 56.0%, 35.3% and 96.6% respectively. For convalescent sera, the sensitivity, specificity, PPV and NPV of the MAC-ELISA assay were 93.3%, 51.5%, 63.6% and 89.5% respectively. For paired sera, the sensitivity, specificity, PPV and NPV of the MAC-ELISA assay were 93.6%, 37.5%, 59.2%, 85.7% respectively.

Conclusions

The M20 MAC-ELISA assay performed with a high sensitivity and low specificity in the acute phase of illness. Sensitivity was similar as compared with MAT in the convalescent phase and specificity remained low. Paired sera were the most sensitive but least specific by comparison to MAT serodiagnosis. NPV for acute, convalescent and paired sera was high. The limited specificity and high sensitivity of the MAC-ELISA IgM suggests that it would be most valuable to exclude leptospirosis in low-resource regions that lack immediate access to definitive reference laboratory techniques such as MAT.

【 授权许可】

   
2013 Canal et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Lau C, Smythe L, Weinstein P: Leptospirosis: an emerging disease in travellers. Travel Med Infect Dis 2010, 8(1):33-39.
• [2]Levett PN: Leptospirosis. Clin Micro Review 2001, 14(2):296-326.
• [3]Levett PN, Mandel GL, Mandell D: Mandell, Douglas & Bennett's Principles and Practice of Infectious Diseases. 7th edition. Philidelphia, PA: Elsevier Publishing Co; 2010. Chapter 216
• [4]Bharti AR, et al.: Leptospirosis: a zoonotic disease of global importance. Lancet Infect Dis 2003, 3(12):757-771.
• [5]Toyokawa T, Ohnishi M, Koizumi N: Diagnosis of acute leptospirosis. Expert Rev Anti Infect Ther 2011, 9(1):111-121.
• [6]Vinetz JM: Ten Common Questions About Leptospirosis. Infect Dis Clin Pract 2000, 9(2):59-65.
• [7]Brockmann S, et al.: Outbreak of leptospirosis among triathlon participants in Germany, 2006. BMC Infect Dis 2010, 10:91. BioMed Central Full Text
• [8]Russell KL, et al.: An outbreak of leptospirosis among Peruvian military recruits. Am J Trop Med Hyg 2003, 69(1):53-57.
• [9]Wright H, Goot K, Rogers B: Spirochaetes and sunshine: leptospirosis in the aftermath of the Queensland floods. Med J Aust 2012, 196(8):500-502.
• [10]Levett PN, et al.: Detection of pathogenic leptospires by real-time quantitative PCR. J Med Microbiol 2005, 54(Pt 1):45-49.
• [11]Cumberland P, Everard CO, Levett PN: Assessment of the efficacy of an IgM-elisa and microscopic agglutination test (MAT) in the diagnosis of acute leptospirosis. Am J Trop Med Hyg 1999, 61(5):731-734.
• [12]Levett PN, Branch SL: Evaluation of two enzyme-linked immunosorbent assay methods for detection of immunoglobulin M antibodies in acute leptospirosis. Am J Trop Med Hyg 2002, 66(6):745-748.
• [13]Bajani MD, et al.: Evaluation of four commercially available rapid serologic tests for diagnosis of leptospirosis. J Clin Microbiol 2003, 41(2):803-809.
• [14]Chirathaworn C, et al.: Comparison of a slide agglutination test, LeptoTek Dri-Dot, and IgM-ELISA with microscopic agglutination test for Leptospira antibody detection. Southeast Asian J Trop Med Public Health 2007, 38(6):1111-1114.
• [15]Johnson MA, et al.: Environmental exposure and leptospirosis. Peru. Emerg Infect Dis 2004, 10(6):1016-1022.
• [16]Forshey BM, et al.: Arboviral etiologies of acute febrile illnesses in Western South America, 2000–2007. PLoS Negl Trop Dis 2010, 4(8):e787.
• [17]Roshanravan B, et al.: Endemic malaria in the Peruvian Amazon region of Iquitos. Am J Trop Med Hyg 2003, 69(1):45-52.
• [18]Santana Vdos S, et al.: Concurrent Dengue and malaria in the Amazon region. Rev Soc Bras Med Trop 2010, 43(5):508-511.
• [19]Manock SR, et al.: Etiology of acute undifferentiated febrile illness in the Amazon basin of Ecuador. Am J Trop Med Hyg 2009, 81(1):146-151.
• [20]Ganoza CA, et al.: Determining risk for severe leptospirosis by molecular analysis of environmental surface waters for pathogenic Leptospira. PLoS Med 2006, 3(8):e308.
• [21]Norman AF, et al.: Differentiation of Bartonella-like isolates at the species level by PCR-restriction fragment length polymorphism in the citrate synthase gene. J Clin Microbiol 1995, 33(7):1797-1803.
• [22]Cole JR Jr, Sulzer CR, Pursell AR: Improved microtechnique for the leptospiral microscopic agglutination test. Appl Microbiol 1973, 25(6):976-980.
• [23]Stern EJ, et al.: Outbreak of leptospirosis among Adventure Race participants in Florida, 2005. Clin Infect Dis 2010, 50(6):843-849.
• [24]World Health Organisation: Human leptospirosis: guidance for diagnosis, surveillance and control. Geneva, Switzerland: WHO; 2003.
• [25]Blanco RM, Takei K, Romero EC: Leptospiral glycolipoprotein as a candidate antigen for serodiagnosis of human leptospirosis. Lett Appl Microbiol 2009, 49(2):267-273.
• [26]Pinne M, Haake DA: A comprehensive approach to identification of surface-exposed, outer membrane-spanning proteins of Leptospira interrogans. PLoS One 2009, 4(6):e6071.
• [27]Thongboonkerd V: Proteomics in leptospirosis research: towards molecular diagnostics and vaccine development. Expert Rev Mol Diagn 2008, 8(1):53-61.
• [28]Felgner P: Serodiagnostic antigen discovery for leptospirosis disease (Scientific Oral Presentation). Philadelphia; 2011. [American Society of Tropical Medicine and Hygiene]