Abstract
The search for valuable early diagnostic markers for leptospirosis is ongoing. The aim of the present study was to evaluate the diagnostic value of macrophage migration inhibitory factor (MIF) for leptospirosis. MIF is an immunoregulatory cytokine secreted by a variety of cell types involved in immune response and the pathogenesis of various diseases. It was previously described as a severity predictor of diseases. Samples of 142 leptospirosis cases, 101 other febrile cases, and 57 healthy controls were studied. The prevalence of leptospirosis was 47.3%. Autumnalis, Australis, and Canicola were the highly prevalent leptospiral serovars with a microscopic agglutination test (MAT) titer in the range 1:80–1:2,560. Enzyme-linked immunosorbent assay (ELISA) of MIF was carried out to measure the serum MIF levels. We found that the serum MIF levels [median, (interquartile range)] were significantly (p < 0.001) elevated in different clinical forms of leptospirosis, such as febrile illness [7.5 ng/ml (5.32–8.97)], pulmonary hemorrhage [13.2 ng/ml (11.77–16.72)], Weil’s syndrome [8.8 ng/ml (7.25–9.95)], and renal failure [8.6 ng/ml (7.18–10.5)], than in healthy controls [0.65n g/ml (0.5–1.1)]. Serum MIF had sensitivity, specificity, positive predictive value, and negative predictive value of 100%, >90%, >90%, and 100%, respectively. Receiver operating characteristic (ROC) analysis revealed that the serum MIF levels between leptospirosis cases and control subjects had an area under the curve (AUC) value of >0.9 (p < 0.0001). In leptospirosis patients, elevation of serum MIF was significantly (p < 0.001) higher in severe cases with organ dysfunction [10 ng/ml (7.8–14.5)] than that in mild febrile cases [7.5 ng/ml (5.32–8.97)], with the difference of 2.5 indicating that serum MIF acts as a predictor of leptospirosis severity. Pearson’s correlation test demonstrated that the serum MIF level was strongly correlated (r = 0.75, p < 0.0001) with disease progression. The median lethal dose (LD50) of leptospiral lipopolysaccharide (LPS) in BALB/c mice was determined to be 20 mg/kg, which gave rise to endotoxemia. Leptospiral LPS triggered the upregulation of MIF expression at 24 h post-infection, which reached the peak level at 24 h post-treatment in THP-1 cells and showed elevated MIF expressions in different tissues of BALB/c mice at the early stage of infection. Taken together, MIF is an early-phase cytokine that could serve as a rapid diagnostic marker for leptospirosis.
Highlights
Leptospirosis is a spirochaetal zoonotic disease caused by pathogenic leptospires infecting both humans and animals
We propose the consideration of serum macrophage migration inhibitory factor (MIF) for the diagnosis of leptospirosis because the expression of MIF is significantly elevated at the early stage of disease induction
A case–control study was conducted to estimate the prevalence of leptospirosis in Tiruchirappalli, to determine the serum levels of MIF in leptospirosis patients compared with other febrile cases and healthy control subjects, and to assess the leptospiral lipopolysaccharide (LPS)-mediated MIF upregulation in in vitro and in vivo experimental models
Summary
Leptospirosis is a spirochaetal zoonotic disease caused by pathogenic leptospires infecting both humans and animals. It has a spectrum of clinical presentations ranging from selflimiting mild, nonspecific flu-like illness, to severe fatal conditions (Haake and Levett, 2015). The signs and symptoms of leptospirosis simulate those of well-known diseases such as typhoid, dengue, malaria, and acute hepatitis (Safa et al, 2017), leading to underdiagnosis and inadequate timely treatment (Izurieta et al, 2008). The two major limitations that complicate leptospirosis management are the lack of knowledge on the importance of disease considerations and the lack of early and accurate diagnostic tools. Frequent estimation of the disease prevalence in tropical regions and the development of early diagnostic markers are urgently needed
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
