Abstract
BackgroundVisceral leishmaniasis (VL), caused by protozoa of the Leishmania donovani complex, is a widespread parasitic disease of great public health importance; without effective chemotherapy symptomatic VL is usually fatal. Distinction of asymptomatic carriage from progressive disease and the prediction of relapse following treatment are hampered by the lack of prognostic biomarkers for use at point of care.Methodology/Principal FindingsAll IgG subclass and IgG isotype antibody levels were determined using unpaired serum samples from Indian and Sudanese patients with differing clinical status of VL, which included pre-treatment active VL, post-treatment cured, post-treatment relapsed, and post kala-azar dermal leishmaniasis (PKDL), as well as seropositive (DAT and/or rK39) endemic healthy controls (EHCs) and seronegative EHCs. L. donovani antigen-specific IgG1 levels were significantly elevated in relapsed versus cured VL patients (p<0.0001). Using paired Indian VL sera, consistent with the known IgG1 half-life, IgG1 levels had not decreased significantly at day 30 after the start of treatment (p = 0.8304), but were dramatically decreased by 6 months compared to day 0 (p = 0.0032) or day 15 (p<0.0001) after start of treatment. Similarly, Sudanese sera taken soon after treatment did not show a significant change in the IgG1 levels (p = 0.3939). Two prototype lateral flow immunochromatographic rapid diagnostic tests (RDTs) were developed to detect IgG1 levels following VL treatment: more than 80% of the relapsed VL patients were IgG1 positive; at least 80% of the cured VL patients were IgG1 negative (p<0.0001).Conclusions/SignificanceSix 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.
Highlights
The leishmaniases are widespread neglected infectious diseases of major public health importance, caused by protozoan parasites of the Leishmania (Leishmania) and Leishmania (Viannia) subgenera
In this work we investigated the association of clinical status of Visceral leishmaniasis (VL) patients with subclasses of the IgG antibody response made to L. donovani infection
The IgG1 subclass responses gave discrete separations between cured versus active VL and relapsed VL (Figure 1A and 1B). This potential human IgG1 subclass association with clinical VL status was investigated further, in particular to determine whether it could be suitable for development as a rapid diagnostic test (RDT) to detect relapsed VL patients at point of care (POC)
Summary
The leishmaniases are widespread neglected infectious diseases of major public health importance, caused by protozoan parasites of the Leishmania (Leishmania) and Leishmania (Viannia) subgenera. VL is caused by protozoan (unicellular) parasites of the Leishmania donovani complex, transmitted to humans when an infected sandfly takes a bloodmeal. In this work we investigated the association of clinical status of VL patients (active pre-treatment, and those deemed cured or relapsed post-treatment) with subclasses of the IgG antibody response made to L. donovani infection. Visceral leishmaniasis (VL), caused by protozoa of the Leishmania donovani complex, is a widespread parasitic disease of great public health importance; without effective chemotherapy symptomatic VL is usually fatal. Distinction of asymptomatic carriage from progressive disease and the prediction of relapse following treatment are hampered by the lack of prognostic biomarkers for use at point of care
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