Prognostic Biomarker Found for Post-Chemotherapeutic Relapse in Visceral Leishmaniasis

By LabMedica International staff writers
Posted on 06 Nov 2014
The effective clinical management, chemotherapy and control of the transmission of visceral leishmaniasis (VL) are largely dependent on early and unequivocal diagnosis as without effective chemotherapy symptomatic VL is usually fatal.

The most sensitive and specific method to detect the causative agent of VL is microscopic examination of invasive spleen aspirates; bone marrow and lymph node aspirates provide similar high specificity but lesser sensitivity although more user-friendly point-of-care (POC) diagnostics have been developed based on antibody detection.

Image: The MRX II microplate reader (Photo courtesy of Dynex Technologies).

Scientists at the London School of Hygiene and Tropical Medicine (UK) and their international colleagues collected plasma samples after 2007 from active VL, cured, relapsed, post-kala-azar dermal leishmaniasis (PKDL) and asymptomatic groups from the endemic region of Bihar state (north-eastern India), and control subjects from a region where VL is not endemic. Serum samples were also collected in 2011 and 2013, from active VL, treated, relapsed, PKDL, and endemic controls in eastern Sudan.

Leishmania donovani specific enzyme-linked immunosorbent assays (ELISA) were performed and human immunoglobulin G (IgG) isotype responses were determined. The ELISAs were read at 490 nm on a Spectra Max 190 microplate reader (Molecular Devices; Sunnyvale, CA, USA), the MRX II plate reader, (Dynex Technologies; Chantilly, USA). Prototype L. donovani antigen-specific IgG1 immunochromatographic rapid diagnostic tests (RDTs) were developed and consisted of a cassette with a nitrocellulose membrane, a sample pad, a conjugate pad and an absorbent pad, backed with a plastic strip.

For the Indian VL sera, consistent with the known IgG1 half-life, IgG1 levels had not decreased significantly at day 30 after the start of treatment, but were dramatically decreased by six months compared to day 0 or day 15 after the start of treatment. Similarly, Sudanese sera taken soon after treatment did not show a significant change in the IgG1 levels. The two prototype lateral flow immunochromatographic rapid diagnostic tests that were developed to detect IgG1 levels following VL treatment showed that in more than 80% of the relapsed VL patients, they were IgG1 positive; while in at least 80% of the cured VL patients were IgG1 negative.

The authors concluded that six months after treatment of active VL, elevated levels of specific IgG1 were associated with treatment failure and relapse, whereas no IgG1 or low levels were detected in cured VL patients. A lateral flow RDT was successfully developed to detect anti-Leishmania IgG1 as a potential biomarker of post-chemotherapeutic relapse.

Related Links:

London School of Hygiene and Tropical Medicine 
Molecular Devices
Dynex Technologies 



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