Browsing by Author "Bruno C. Bremer Hinckel"

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Detection of Immunoglobulin G1 against rK39 Improves Monitoring of Treatment Outcomes in Visceral Leishmaniasis
(Oxford University Press, 2019) Guy Mollett; Bruno C. Bremer Hinckel; Tapan Bhattacharyya; Tegwen Marlais; Om Prakash Singh; Pascal Mertens; Andrew K. Falconar; Sayda El-Safi; Shyam Sundar; Michael A. Miles
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 the outcomes of treatments. Previous investigations using Leishmania lysate antigen demonstrated that the immunoglobulin (Ig) G1 response is a potential indicator of a patient's clinical status after chemotherapy. Methods: IgG1 or IgG enzyme-linked immunosorbent assays (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 postchemotherapy (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 conjugates gave a far more discriminative decrease in post-treatment antibody responses when compared to IgG (P <. 0001). Novel IgG1 rK39 RDTs provided strong evidence for decreased IgG1 responses in patients who had successful treatment (P <. 0001). Furthermore, both IgG1 rK39 RDTs (n = 38) and ELISAs showed a highly significant difference in test outcomes between cured patients and those who relapsed (n = 23; P <. 0001). RDTs were more sensitive than corresponding ELISAs. Conclusions: We present strong evidence for the use of IgG1 in monitoring treatment outcomes in VL, and the first use of an IgG1-based RDT using the 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. © 2018 The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America.
Visceral Leishmaniasis IgG1 Rapid Monitoring of Cure vs. Relapse, and Potential for Diagnosis of Post Kala-Azar Dermal Leishmaniasis
(Frontiers Media S.A., 2018) Tegwen Marlais; Tapan Bhattacharyya; Om Prakash Singh; Pascal Mertens; Quentin Gilleman; Caroline Thunissen; Bruno C. Bremer Hinckel; Callum Pearson; Bathsheba L. Gardner; Stephanie Airs; Marianne de la Roche; Kiera Hayes; Hannah Hafezi; Andrew K. Falconar; Osama Eisa; Alfarazdeg Saad; Basudha Khanal; Narayan Raj Bhattarai; Suman Rijal; Marleen Boelaert; Sayda El-Safi; Shyam Sundar; Michael A. Miles
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. © Copyright © 2018 Marlais, Bhattacharyya, Singh, Mertens, Gilleman, Thunissen, Hinckel, Pearson, Gardner, Airs, de la Roche, Hayes, Hafezi, Falconar, Eisa, Saad, Khanal, Bhattarai, Rijal, Boelaert, El-Safi, Sundar and Miles.