Dengue virus infected patients can generate false positives in the ‘gold standard’ Leptospira spp. microscopic agglutination test (MAT) and IgG- and IgM- antibody specific immunofluorescence and protein (Western) immunoblot assays due to cross-reactions with their outer surface membrane proteins: Public health concern

IF 4 3区医学 Q1 INFECTIOUS DISEASES

Journal of Infection and Public Health Pub Date : 2025-09-19 DOI:10.1016/j.jiph.2025.102975

Claudia M. Romero-Vivas, Lissette Hernández Arrieta, Margarett Cuello-Pérez, Andrew K. Falconar

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Abstract

Background

The dengue viruses (DENVs) and Leptospira spp. both cause large numbers of human infections and fatalities within their widely overlapping distributions, thereby requiring differential diagnoses for appropriate patient therapies.

Methods

Many paired acute (S1) and convalescent (S2) phase patients’ sera were tested as potential on-going DENV infections by their IgM and/or IgG antibody reactions and DENV isolations and serotype determinations. The sera from these DENV-confirmed cases were further tested for their abilities to cross-react with the Leptospira spp. of different serovars in the ‘gold standard’ microscopic agglutination test (MAT), immunofluorescence assays (IFAs), IgM-ELISA and protein (Western) immunoblot assays, as well as Leptospira spp. isolation and PCR tests.

Results

In this study, 35 % of these patients’ sera were confirmed as on-going DENV infections by their dramatically (>> 4-fold S1 to S2) increased anti-DENV IgM and/or IgG antibody ELISA titres. Of those, 8.6 % also displayed high S2 and/or ≥ 4-fold increased S1 to S2 serum titres using the Leptospira spp. MAT due to their IgM and/or IgG cross-reactions with their 68–72, 38–42 and 18–22 kDa outer surface membrane proteins (OSMPs) identified by SDS-PAGE and protein (Western) blotting after Triton X-114 detergent phase-separations. DENV-1, −2 or −3 serotypes, but not Leptospira spp., were isolated and their sera were negative using a Leptospira spp.-specific PCR and commercial anti-Leptospira spp. IgM-specific ELISA.

Conclusions

This is the first report of false-positive anti-Leptospira spp. IgM and/or IgG antibody reactions resulting from on-going primary or secondary DENV infections which may: a) account for some ‘DENV-Leptospira spp. co-infections’ being erroneously reported and b) lead to inappropriate antibiotic therapies, rather than appropriate early supportive therapy for ‘severe dengue’ cases in their widely co-endemic pan-global regions.

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登革病毒感染患者可能在钩端螺旋体显微凝集试验（MAT）和IgG和IgM抗体特异性免疫荧光和蛋白（Western）免疫印迹检测中产生假阳性，因为它们与外表面膜蛋白发生交叉反应：公共卫生问题

登革热病毒（denv）和钩端螺旋体在其广泛重叠的分布范围内都引起大量人类感染和死亡，因此需要鉴别诊断以进行适当的患者治疗。方法对多例急性期（S1）和恢复期（S2）患者血清进行IgM和/或IgG抗体反应、DENV分离和血清型检测，作为潜在的DENV感染。对这些denv确诊病例的血清进行“金标准”显微凝集试验（MAT）、免疫荧光试验（IFAs）、IgM-ELISA和蛋白（Western）免疫印迹试验，以及钩端螺旋体分离和PCR试验，进一步检测其与不同血清型钩端螺旋体交叉反应的能力。结果在本研究中，35 %的患者血清中抗DENV IgM和/或IgG抗体ELISA效价显著（S1到S2的4倍）升高，证实为DENV持续感染。其中，8.6 %也显示出较高的S2和/或≥ 4倍的血清S1到S2滴度，这是由于在Triton X-114洗涤剂相分离后，通过SDS-PAGE和蛋白（Western）印迹法鉴定出它们的68 - 72,38 - 42和18-22 kDa外表面膜蛋白（OSMPs）与IgM和/或IgG交叉反应。分离到DENV-1、−2或−3血清型，但未分离到钩端螺旋体，用钩端螺旋体特异性PCR和商用抗钩端螺旋体igm特异性ELISA检测血清均为阴性。结论：这是首次报道由持续的原发性或继发性登革病毒感染引起的抗钩端螺旋体IgM和/或IgG抗体反应假阳性，这可能：a)解释了一些“登革病毒-钩端螺旋体共感染”的错误报告；b)导致不适当的抗生素治疗，而不是在广泛共流行的泛全球地区对“严重登革热”病例进行适当的早期支持治疗。

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来源期刊

Journal of Infection and Public Health PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH -INFECTIOUS DISEASES

CiteScore

13.10

自引率

1.50%

发文量

203

审稿时长

96 days

期刊介绍： The Journal of Infection and Public Health, first official journal of the Saudi Arabian Ministry of National Guard Health Affairs, King Saud Bin Abdulaziz University for Health Sciences and the Saudi Association for Public Health, aims to be the foremost scientific, peer-reviewed journal encompassing infection prevention and control, microbiology, infectious diseases, public health and the application of healthcare epidemiology to the evaluation of health outcomes. The point of view of the journal is that infection and public health are closely intertwined and that advances in one area will have positive consequences on the other. The journal will be useful to all health professionals who are partners in the management of patients with communicable diseases, keeping them up to date. The journal is proud to have an international and diverse editorial board that will assist and facilitate the publication of articles that reflect a global view on infection control and public health, as well as emphasizing our focus on supporting the needs of public health practitioners. It is our aim to improve healthcare by reducing risk of infection and related adverse outcomes by critical review, selection, and dissemination of new and relevant information in the field of infection control, public health and infectious diseases in all healthcare settings and the community.