Detection of IgG1 against rK39 improves monitoring of treatment outcome in visceral leishmaniasis.

Background: Visceral leishmaniasis (VL), caused by the Leishmania donovani complex, is a fatal neglected tropical disease that is targeted for elimination in India, Nepal and Bangladesh. Improved diagnostic tests are required for early case detection and for monitoring outcome of treatment. Previous investigations using Leishmania lysate antigen demonstrated that IgG1 response is a potential indicator of clinical status after chemotherapy.

Methods: IgG1 or IgG ELISAs with rK39 or lysate antigens, and novel IgG1 rK39 rapid diagnostic tests (RDTs) were assessed with Indian VL serum samples from the following clinical groups: paired pre- and post-chemotherapy (deemed cured); relapsed; other infectious diseases, and endemic healthy controls.

Results: With paired pre- and post-treatment samples (n = 37 pairs), ELISAs with rK39 and IgG1-specific conjugate gave a far more discriminative decrease in post-treatment antibody response when compared to IgG (p <0.0001). Novel IgG1 rK39 RDTs provided strong evidence for decreased IgG1 response in patients who had successful treatment (p <0.0001). Furthermore, both IgG1 rK39 RDTs (n = 38) and ELISAs showed a highly significant difference in test outcome between cured patients and those who relapsed (n = 23) (p <0.0001). RDTs were more sensitive than corresponding ELISAs.

Conclusions: We present here strong evidence for the use of IgG1 in monitoring treatment outcome in VL, and the first use of an IgG1-based RDT using rK39 antigen for the discrimination of post-treatment cure versus relapse in VL. Such an RDT may have a significant role in monitoring patients and in targeted control and elimination of this devastating disease.