Urinary leptospiral sphingomyelinases as diagnostic markers of leptospirosis in dengue patients co-infected with leptospirosis

Abstract

The study aims to evaluate the diagnostic potential of pathogen-specific leptospiral sphingomyelinases, LipL32, LipL41, and HbpA in human patients with dengue-leptospirosis coinfection. Patients (n-86), upon clinical evaluation, were categorized into Group I (n-37; leptospirosis), Group II (n-39; dengue-leptospirosis coinfection), and Group III (n-10; negative for both dengue and leptospirosis). ELISA identified significant levels of the four leptospiral antigens in the urine of Group I and II, but not in Group III patients. Immunoblot analysis of the urinary proteins with specific antibodies identified the tissue-damaging true sphingomyelinases Sph2 and pore-forming SphH. Urinary leptospiral antigens identified patients with leptospirosis and with dengue-leptospirosis coinfection. Patients with renal damage and proteinuria showed high urinary excretion of anti-leptospiral antibodies, with markedly low values in the serum. Proteinuria resulted in the loss of the circulating proteins, reflected by the low levels of anti-leptospiral antibodies in serum, with urine showing albumin and high levels of anti-leptospiral antibodies. IMPORTANCE: The study highlights the diagnostic potential of all four leptospiral antigens. Since early detection of urinary sphingomyelinases is possible, their diagnostic and prognostic potential can be evaluated on a larger sample size. Non-invasive, point-of-care diagnostic devices can be developed for use in endemic regions, particularly during monsoon seasons.

Keywords: Dengue; HbpA; Leptospira; Leptospirosis; Lip41; LipL32; Sphingomyelinase; Urinary antigens.