Visceral Leishmaniasis IgG1 Rapid Monitoring of Cure vs. Relapse, and Potential for Diagnosis of Post Kala-Azar Dermal Leishmaniasis

Abstract

Background: There is a recognized need for an improved diagnostic test to assess post-chemotherapeutic treatment outcome in visceral leishmaniasis (VL) and to diagnose post kala-azar dermal leishmaniasis (PKDL). We previously demonstrated by ELISA and a prototype novel rapid diagnostic test (RDT), that high anti-Leishmania IgG1 is associated with post-treatment relapse versus cure in VL.Methodology: Here, we further evaluate this novel, low-cost RDT, named VL Sero K-SeT, and ELISA for monitoring IgG1 levels in VL patients after treatment. IgG1 levels against L. donovani lysate were determined. We applied these assays to Indian sera from cured VL at 6 months post treatment as well as to relapse and PKDL patients. Sudanese sera from pre- and post-treatment and relapse were also tested.Results: Of 104 paired Indian sera taken before and after treatment for VL, when deemed clinically cured, 81 (77.9%) were positive by VL Sero K-SeT before treatment; by 6 months, 68 of these 81 (84.0%) had a negative or reduced RDT test line intensity. ELISAs differed in positivity rate between pre- and post-treatment (p = 0.0162). Twenty eight of 33 (84.8%) Indian samples taken at diagnosis of relapse were RDT positive. A comparison of Indian VL Sero K-SeT data from patients deemed cured and relapsed confirmed that there was a significant difference (p < 0.0001) in positivity rate for the two groups using this RDT. Ten of 17 (58.8%) Sudanese sera went from positive to negative or decreased VL Sero K-SeT at the end of 11–30 days of treatment. Forty nine of 63 (77.8%) PKDL samples from India were positive by VL Sero K-SeT.Conclusion: We have further shown the relevance of IgG1 in determining clinical status in VL patients. A positive VL Sero K-SeT may also be helpful in supporting diagnosis of PKDL. With further refinement, such as the use of specific antigens, the VL Sero K-SeT and/or IgG1 ELISA may be adjuncts to current VL control programmes.

Diagnostic accuracy of direct agglutination test, rK39 ELISA and six rapid diagnostic tests among visceral leishmaniasis patients with and without HIV coinfection in Ethiopia

“…The only antigen detecting test evaluated here did not prove valuable because of its very low specificity. Previously, IgG1 was found to be the predominant antibody present in VL infection and has been explored as a potential biomarker of post-chemotherapeutic relapse [ 34 , 35 ]. Therefore it was hypothesized that IgG1 detection may also be useful in predicting progression to VL infection among asymptomatic patients which was previously supported by some limited data [ 35 ].…”

In transition: current health challenges and priorities in Sudan

“…Gold-standard diagnosis by detection of the parasite in tissue specimens is not possible in most rural health facilities. Rapid serological tests provide an alternative, but the rK39 antigen-based test has proven less sensitive in Sudan than in the Indian subcontinent32 and the test has a relatively short shelf-life which can make it uneconomical to keep supplies outside of major centres 33. Ongoing work has been seeking to address the need for cheap, sensitive, specific and sustainable rapid diagnostics for Sudanese visceral leishmaniasis, which will help to better define disease burden, identify cases for prompt treatment and potentially allow confirmation of post-treatment cure 32–34…”

Biomarkers in Post-kala-azar Dermal Leishmaniasis

“…Evaluation in PKDL showed that the VL sero K-set and IgG1 ELISA supported PKDL diagnosis with a strong correlation with post VL samples, suggesting persistence of antibodies after VL. No association was found between elevated IgG1 and macular or polymorphic PKDL lesions (Marlais et al, 2018). IgG1 levels did not show a consistent decrease 1 year after PKDL treatment (Marlais et al, 2018).…”

“…No association was found between elevated IgG1 and macular or polymorphic PKDL lesions (Marlais et al, 2018). IgG1 levels did not show a consistent decrease 1 year after PKDL treatment (Marlais et al, 2018).…”